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Khalil M, Di Ciaula A, Mahdi L, Jaber N, Di Palo DM, Graziani A, Baffy G, Portincasa P. Unraveling the Role of the Human Gut Microbiome in Health and Diseases. Microorganisms 2024; 12:2333. [PMID: 39597722 PMCID: PMC11596745 DOI: 10.3390/microorganisms12112333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/12/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024] Open
Abstract
The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host at both the gut and systemic levels. The gut microbiome, which is primarily made up of commensal bacteria, is critical for maintaining the healthy host's immune system, aiding digestion, synthesizing essential nutrients, and protecting against pathogenic bacteria, as well as influencing endocrine, neural, humoral, and immunological functions and metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter the gut microbiome, resulting in dysbiosis and microbial dysfunction, which can contribute to a variety of noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, cancer, and irritable bowel syndrome. While most evidence to date is observational and does not establish direct causation, ongoing clinical trials and advanced genomic techniques are steadily enhancing our understanding of these intricate interactions. This review will explore key aspects of the relationship between gut microbiota, eubiosis, and dysbiosis in human health and disease, highlighting emerging strategies for microbiome engineering as potential therapeutic approaches for various conditions.
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Affiliation(s)
- Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Laura Mahdi
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Nour Jaber
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Domenica Maria Di Palo
- Division of Hygiene, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Annarita Graziani
- Institut AllergoSan Pharmazeutische Produkte Forschungs- und Vertriebs GmbH, 8055 Graz, Austria;
| | - Gyorgy Baffy
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02130, USA;
- Section of Gastroenterology, Department of Medicine, VA Boston Healthcare System, Boston, MA 02130, USA
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
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Pang C, Dong P, Yang J, Fan Z, Cheng Z, Zhan H. Non-alcoholic fatty pancreas disease: an updated review. JOURNAL OF PANCREATOLOGY 2024; 7:212-221. [DOI: 10.1097/jp9.0000000000000157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Ectopic accumulation of fat can cause a variety of metabolic diseases, and the emerging non-alcoholic fatty pancreas disease (NAFPD) is increasingly being recognized by clinicians as a cause for concern. NAFPD is a disease caused by abnormal accumulation of adipose tissue in the pancreas, which is related to obesity. The main feature of NAFPD is death of acinar cells, which are then replaced by adipose cells. However, the underlying molecular mechanisms have not been fully explored. Obesity, aging, and metabolic syndrome are independent risk factors for the occurrence and development of NAFPD. Studies have shown that NAFPD leads to insulin resistance and pancreatic dysfunction, increases the risk of diabetes mellitus, worsens the severity of pancreatitis, and is significantly correlated with pancreatic cancer and postoperative pancreatic fistula. There is no standard treatment for NAFPD; exercise, a balanced diet, and lifestyle can help reduce pancreatic fat; however, other treatment modalities such as drugs and bariatric surgery are still being explored. The specific pathological mechanism of NAFPD remains unclear, and its potential association with various clinical diseases requires further study. This review summarizes the etiology, diagnosis, clinical consequences, and potential therapeutic strategies of NAFPD.
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Affiliation(s)
- Chaoyu Pang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Peng Dong
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Jian Yang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiqiang Cheng
- Division of Colorectal Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
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Garruti G, Baj J, Cignarelli A, Perrini S, Giorgino F. Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis. Front Endocrinol (Lausanne) 2023; 14:1154561. [PMID: 37274345 PMCID: PMC10236950 DOI: 10.3389/fendo.2023.1154561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 04/07/2023] [Indexed: 06/06/2023] Open
Abstract
Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.
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Affiliation(s)
- Gabriella Garruti
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Jacek Baj
- Department of Anatomy, Medical University of Lublin, Lublin, Poland
| | - Angelo Cignarelli
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Sebastio Perrini
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Francesco Giorgino
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
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Truong E, Pandol S, Jeon C. Uniting epidemiology and experimental models: pancreatic steatosis and pancreatic cancer. EBioMedicine 2022; 79:103996. [PMID: 35405390 PMCID: PMC9010750 DOI: 10.1016/j.ebiom.2022.103996] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/07/2022] [Accepted: 03/28/2022] [Indexed: 02/07/2023] Open
Abstract
Research from epidemiologic studies and experimental animal models provide insights into the role of pancreatic steatosis in the development of pancreatic cancer. Epidemiologic data demonstrate that pancreatic steatosis is widely prevalent and significantly associated with both development and progression of pancreatic cancer. By focusing on current experimental models, this review elucidates potential cellular mechanisms underlying not only the pathophysiology of pancreatic steatosis itself, but also the pathogenesis behind pancreatic steatosis's role in changing the tumour microenvironment and accelerating the development of pancreatic cancer. This review further explores the impact of bariatric surgery on pancreatic steatosis and pancreatic cancer. Synthesizing knowledge from both epidemiologic studies and experimental animal models, this review identifies gaps in current knowledge regarding pancreatic steatosis and its role in carcinogenesis and proposes future research directions to elucidate the possible mechanisms underlying other obesity-associated cancers.
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Affiliation(s)
- Emily Truong
- Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, California.
| | - Stephen Pandol
- Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, California
| | - Christie Jeon
- Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, California; UCLA Fielding School of Public Health, Los Angeles, CA
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Catalán V, Avilés-Olmos I, Rodríguez A, Becerril S, Fernández-Formoso JA, Kiortsis D, Portincasa P, Gómez-Ambrosi J, Frühbeck G. Time to Consider the "Exposome Hypothesis" in the Development of the Obesity Pandemic. Nutrients 2022; 14:1597. [PMID: 35458158 PMCID: PMC9032727 DOI: 10.3390/nu14081597] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/04/2022] [Accepted: 04/08/2022] [Indexed: 02/04/2023] Open
Abstract
The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent the main contributors to the obesity problem, they are not able to fully explain all cases and current trends. In this context, a body of knowledge related to exposure to as yet underappreciated obesogenic factors, which can be referred to as the "exposome", merits detailed analysis. Contrarily to the genome, the "exposome" is subject to a great dynamism and variability, which unfolds throughout the individual's lifetime. The development of precise ways of capturing the full exposure spectrum of a person is extraordinarily demanding. Data derived from epidemiological studies linking excess weight with elevated ambient temperatures, in utero, and intergenerational effects as well as epigenetics, microorganisms, microbiota, sleep curtailment, and endocrine disruptors, among others, suggests the possibility that they may work alone or synergistically as several alternative putative contributors to this global epidemic. This narrative review reports the available evidence on as yet underappreciated drivers of the obesity epidemic. Broadly based interventions are needed to better identify these drivers at the same time as stimulating reflection on the potential relevance of the "exposome" in the development and perpetuation of the obesity epidemic.
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Affiliation(s)
- Victoria Catalán
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (V.C.); (A.R.); (S.B.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31008 Pamplona, Spain;
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
| | - Iciar Avilés-Olmos
- Department of Neurology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Amaia Rodríguez
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (V.C.); (A.R.); (S.B.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31008 Pamplona, Spain;
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
| | - Sara Becerril
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (V.C.); (A.R.); (S.B.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31008 Pamplona, Spain;
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
| | | | - Dimitrios Kiortsis
- Department of Nuclear Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece;
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Javier Gómez-Ambrosi
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (V.C.); (A.R.); (S.B.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31008 Pamplona, Spain;
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
| | - Gema Frühbeck
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (V.C.); (A.R.); (S.B.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31008 Pamplona, Spain;
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain
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Pancreatic Steatosis Is Associated with Both Metabolic Syndrome and Pancreatic Stiffness Detected by Ultrasound Elastography. Dig Dis Sci 2022; 67:293-304. [PMID: 33651254 DOI: 10.1007/s10620-021-06844-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 01/10/2021] [Indexed: 12/16/2022]
Abstract
INTRODUCTION There is increasing evidence that pancreatic steatosis (PS) is associated with metabolic syndrome (MS). However, it is not known whether it is associated with PS grade and pancreatic stiffness, or not. We aimed to evaluate the relationship between PS and its grade detected by transabdominal ultrasound, and pancreatic stiffness determined by two-dimensional shearwave elastography (2D-SWE), whether it has clinical significance and its relationship with MS. METHODS Patients with and without PS were evaluated prospectively. RESULTS Patients with PS had higher odds ratio for MS (OR 5.49). Also, ultrasonographic grade of PS was associated with MS parameters and hepatosteatosis. Pancreatic SWE value was significantly higher in PS group and positively correlated with PS grade, liver fat, MS, number of MS criteria. DISCUSSION/CONCLUSION PS and its grade were associated with MS. In this first comprehensive PS-SWE study, we found that pancreas stiffness increased in the presence of PS, in correlation with PS grade and MS.
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Filippatos TD, Alexakis K, Mavrikaki V, Mikhailidis DP. Nonalcoholic Fatty Pancreas Disease: Role in Metabolic Syndrome, "Prediabetes," Diabetes and Atherosclerosis. Dig Dis Sci 2022; 67:26-41. [PMID: 33469809 DOI: 10.1007/s10620-021-06824-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 01/05/2021] [Indexed: 02/06/2023]
Abstract
Fat accumulation in the pancreas associated with obesity and the metabolic syndrome (MetS) has been defined as "non-alcoholic fatty pancreas disease" (NAFPD). The aim of this review is to describe the association of NAFPD with obesity, MetS, type 2 diabetes mellitus (T2DM) and atherosclerosis and also increase awareness regarding NAFPD. Various methods are used for the detection and quantification of pancreatic fat accumulation that may play a significant role in the differences that have been observed in the prevalence of NAFPD. Endoscopic ultrasound provides detailed images of the pancreas and its use is expected to increase in the future. Obesity and MetS have been recognized as NAFPD risk factors. NAFPD is strongly associated with non-alcoholic fatty liver disease (NAFLD) and it seems that the presence of both may be related with aggravation of NAFLD. A role of NAFPD in the development of "prediabetes" and T2DM has also been suggested by most human studies. Accumulation of fat in pancreatic tissue possibly initiates a vicious cycle of beta-cell deterioration and further pancreatic fat accumulation. Additionally, some evidence indicates a correlation between NAFPD and atherosclerotic markers (e.g., carotid intima-media thickness). Weight loss and bariatric surgery decreases pancreatic triglyceride content but pharmacologic treatments for NAFPD have not been evaluated in specifically designed studies. Hence, NAFPD is a marker of local fat accumulation possibly associated with beta-cell function impairment, carbohydrate metabolism disorders and atherosclerosis.
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Affiliation(s)
- T D Filippatos
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece.
| | - K Alexakis
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - V Mavrikaki
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - D P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, NW3 2QG, UK.,Mohammed Bin Rashid University (MBRU) of Medicine and Health Sciences, Dubai, United Arab Emirates
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Yu Q, Xu T, Ding F, Ding Z, Lin R. Decreased infiltration of adipose tissue macrophages and amplified inflammation of adipose tissue in obese mice with severe acute pancreatitis. Pancreatology 2021; 21:S1424-3903(21)00156-3. [PMID: 34088592 DOI: 10.1016/j.pan.2021.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 04/13/2021] [Accepted: 05/07/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Macrophages are involved in obesity-associated inflammation and severe acute pancreatitis (SAP) development. However, the role of adipose tissue macrophages (ATMs) in obesity-related SAP has not been fully elucidated. We investigated the relationship between ATMs and inflammatory responses in SAP model mice fed a high-fat diet (HFD). METHODS SAP was induced in animal models via intraperitoneal injections of caerulein and lipopolysaccharide (LPS). SAP severity was evaluated, both morphologically and biochemically, and macrophage infiltration in the pancreas and epididymal adipose tissue was measured. We also analyzed apoptosis levels, polarization of the ATMs, and expression of inflammatory mediators in epididymal adipose tissue. RESULTS Obesity increased disease severity in SAP animals. Increased macrophage infiltration in the pancreas induced by SAP was found in both normal diet (ND)- and HFD-fed mice. Total ATM infiltration in epididymal adipose tissue was elevated by HFD, while a significant decrease in infiltration was observed in both the ND + SAP and HFD + SAP groups. The apoptosis levels of ATMs were reduced in the HFD group, but were markedly enhanced in both the ND + SAP and HFD + SAP groups compared to their respective control groups. Higher levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were observed in the HFD + SAP than in the ND + SAP group. Increased proportion of M1 type ATMs was induced by both HFD and SAP. CONCLUSIONS Total ATM infiltration was decreased in epididymal adipose tissue of SAP animals. ATM polarization to the M1 type resulted in an amplified inflammatory response in obese mice with SAP.
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Affiliation(s)
- Qiao Yu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Xu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Feifei Ding
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, 730030, China
| | - Zhen Ding
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Rong Lin
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Di Ciaula A, Portincasa P. Relationships between emissions of toxic airborne molecules and type 1 diabetes incidence in children: An ecologic study. World J Diabetes 2021; 12:673-684. [PMID: 33995854 PMCID: PMC8107975 DOI: 10.4239/wjd.v12.i5.673] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 03/17/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 1 diabetes originates from gene-environment interactions, with increasing incidence over time. AIM To identify correlates of childhood type 1 diabetes in European countries using an ecological approach. Several environmental variables potentially influencing the onset of type 1 diabetes have been previously evaluated. However, the relationships between epidemiologic data and exposure to toxic airborne molecules are scarcely studied. METHODS We employed an ecological model to explore, in a wide time period (1990-2018), associations between type 1 diabetes incidence in 19 European countries (systematic literature review) and the nationwide production of five widely diffused air pollutants: particulate matter < 10 μm (PM10), nitrogen oxides (NO), non-methane volatile organic compounds (VOCs), sulphur oxide (SO2), and ammonia. RESULTS Data confirm a raising incidence of type 1 diabetes in 18 out of 19 explored countries. The average difference (last vs first report, all countries) was +6.9 × 100000/year, with values ranging from -1.4 (Germany) to +16.6 (Sweden) per 100000/year. Although the overall production of pollutants decreased progressively from 1990 to 2018, type 1 diabetes incidence was positively associated with the nationwide emissions of PM10, VOCs, and NO but not with those of SO2 and ammonia. Type 1 diabetes incidence was significantly higher in countries with high emissions than in those with low emissions of PM10 (27.5 ± 2.4 vs 14.6 ± 2.4 × 100000 residents, respectively), VOCs (24.5 ± 4.4 vs 13.2 ± 1.7 × 100000 residents, respectively), and NO (26.6 ± 3 vs 13.4 ± 2.4 × 100000 residents, respectively), but not of SO2 or ammonia. CONCLUSION Evidence justify further studies to explore better links between long-term air quality and type 1 diabetes onset at the individual level, which should include exposures during pregnancy. In this respect, type 1 diabetes could be, at least in part, a preventable condition. Thus, primary prevention policies acting through a marked abatement of pollutant emissions might attenuate future type 1 diabetes incidence throughout Europe.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari 70124, Italy
- International Society of Doctors for Environment (ISDE), Via XXV Aprile n.34 – 52100 Arezzo, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari 70124, Italy
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Portincasa P, Di Ciaula A, Garruti G, Vacca M, De Angelis M, Wang DQH. Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome. Nutrients 2020; 12:3709. [PMID: 33266235 PMCID: PMC7760347 DOI: 10.3390/nu12123709] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 11/25/2020] [Accepted: 11/26/2020] [Indexed: 02/06/2023] Open
Abstract
Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, Piazza G. Cesare 11, 70124 Bari, Italy;
| | - Mirco Vacca
- Dipartimento di Scienze del Suolo, Della Pianta e Degli Alimenti, Università degli Studi di Bari Aldo Moro, 70124 Bari, Italy; (M.V.); (M.D.A.)
| | - Maria De Angelis
- Dipartimento di Scienze del Suolo, Della Pianta e Degli Alimenti, Università degli Studi di Bari Aldo Moro, 70124 Bari, Italy; (M.V.); (M.D.A.)
| | - David Q.-H. Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA;
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Faienza MF, Chiarito M, Molina-Molina E, Shanmugam H, Lammert F, Krawczyk M, D'Amato G, Portincasa P. Childhood obesity, cardiovascular and liver health: a growing epidemic with age. World J Pediatr 2020; 16:438-445. [PMID: 32020441 PMCID: PMC7224053 DOI: 10.1007/s12519-020-00341-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences. DATA SOURCES The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health. RESULTS We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences. CONCLUSIONS The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood.
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Affiliation(s)
- Maria Felicia Faienza
- Section of Pediatrics, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy.
| | - Mariangela Chiarito
- Section of Pediatrics, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Emilio Molina-Molina
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Harshitha Shanmugam
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Marcin Krawczyk
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
- Laboratory of Metabolic Liver Diseases, Center for Preclinical Research, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | | | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
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12
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Quoc Lam B, Shrivastava SK, Shrivastava A, Shankar S, Srivastava RK. The Impact of obesity and diabetes mellitus on pancreatic cancer: Molecular mechanisms and clinical perspectives. J Cell Mol Med 2020; 24:7706-7716. [PMID: 32458441 PMCID: PMC7348166 DOI: 10.1111/jcmm.15413] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 04/24/2020] [Indexed: 01/18/2023] Open
Abstract
The incidence of obesity and type 2 diabetes (T2DM) in the Western world has increased dramatically during the recent decades. According to the American Cancer Society, pancreatic cancer (PC) is the fourth leading cause of cancer‐related death in the United States. The relationship among obesity, T2DM and PC is complex. Due to increase in obesity, diabetes, alcohol consumption and sedentary lifestyle, the mortality due to PC is expected to rise significantly by year 2040. The underlying mechanisms by which diabetes and obesity contribute to pancreatic tumorigenesis are not well understood. Furthermore, metabolism and microenvironment within the pancreas can also modulate pancreatic carcinogenesis. The risk of PC on a population level may be reduced by modifiable lifestyle risk factors. In this review, the interactions of diabetes and obesity to PC development were summarized, and novel strategies for the prevention and treatment of diabetes and PC were discussed.
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Affiliation(s)
- Bao Quoc Lam
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Sushant K Shrivastava
- Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, UP, India
| | - Anju Shrivastava
- Department of Oncology, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Sharmila Shankar
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.,Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.,Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA
| | - Rakesh K Srivastava
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.,Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
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13
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Di Ciaula A, Wang DQH, Portincasa P. Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention. Expert Rev Gastroenterol Hepatol 2019; 13:157-171. [PMID: 30791781 DOI: 10.1080/17474124.2019.1549988] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 11/15/2018] [Indexed: 02/07/2023]
Abstract
Cholesterol gallstone disease have relationships with various conditions linked with insulin resistance, but also with heart disease, atherosclerosis, and cancer. These associations derive from mechanisms active at a local (i.e. gallbladder, bile) and a systemic level and are involved in inflammation, hormones, nuclear receptors, signaling molecules, epigenetic modulation of gene expression, and gut microbiota. Despite advanced knowledge of these pathways, the available therapeutic options for symptomatic gallstone patients remain limited. Therapy includes oral litholysis by the bile acid ursodeoxycholic acid (UDCA) in a small subgroup of patients at high risk of postdissolution recurrence, or laparoscopic cholecystectomy, which is the therapeutic radical gold standard treatment. Cholecystectomy, however, may not be a neutral event, and potentially generates health problems, including the metabolic syndrome. Areas covered: Several studies on risk factors and pathogenesis of cholesterol gallstone disease, acting at a systemic level have been reviewed through a PubMed search. Authors have focused on primary prevention and novel potential therapeutic strategies. Expert commentary: The ultimate goal appears to target the manageable systemic mechanisms responsible for gallstone occurrence, pointing to primary prevention measures. Changes must target lifestyles, as well as experimenting innovative pharmacological tools in subgroups of patients at high risk of developing gallstones.
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Affiliation(s)
- Agostino Di Ciaula
- a Division of Internal Medicine , Hospital of Bisceglie , Bisceglie , Italy
| | - David Q-H Wang
- b Department of Medicine, Division of Gastroenterology and Liver Diseases , Marion Bessin Liver Research Center, Albert Einstein College of Medicine , Bronx , NY , USA
| | - Piero Portincasa
- c Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
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14
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Gasull M, Pumarega J, Kiviranta H, Rantakokko P, Raaschou-Nielsen O, Bergdahl IA, Sandanger TM, Goñi F, Cirera L, Donat-Vargas C, Alguacil J, Iglesias M, Tjønneland A, Overvad K, Mancini FR, Boutron-Ruault MC, Severi G, Johnson T, Kühn T, Trichopoulou A, Karakatsani A, Peppa E, Palli D, Pala V, Tumino R, Naccarati A, Panico S, Verschuren M, Vermeulen R, Rylander C, Nøst TH, Rodríguez-Barranco M, Molinuevo A, Chirlaque MD, Ardanaz E, Sund M, Key T, Ye W, Jenab M, Michaud D, Matullo G, Canzian F, Kaaks R, Nieters A, Nöthlings U, Jeurnink S, Chajes V, Matejcic M, Gunter M, Aune D, Riboli E, Agudo A, Gonzalez CA, Weiderpass E, Bueno-de-Mesquita B, Duell EJ, Vineis P, Porta M. Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. ENVIRONMENTAL RESEARCH 2019; 169:417-433. [PMID: 30529143 DOI: 10.1016/j.envres.2018.11.027] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/16/2018] [Accepted: 11/18/2018] [Indexed: 05/04/2023]
Abstract
BACKGROUND The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
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Affiliation(s)
- Magda Gasull
- Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - José Pumarega
- Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Hannu Kiviranta
- National Institute for Health and Welfare, Department of Health Security, Kuopio, Finland
| | - Panu Rantakokko
- National Institute for Health and Welfare, Department of Health Security, Kuopio, Finland
| | | | - Ingvar A Bergdahl
- Department of Biobank Research, Umeå University, Umeå, Sweden; Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | | | - Fernando Goñi
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Biodonostia Health Research Institute; Public Health Laboratory in Gipuzkoa, Basque Government, San Sebastian, Spain
| | - Lluís Cirera
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain
| | | | - Juan Alguacil
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Universidad de Huelva, Huelva, Spain
| | - Mar Iglesias
- Department of Pathology, Hospital del Mar (PSMar), Barcelona, Spain
| | | | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Francesca Romana Mancini
- CESP, Faculté de Médecine - Univ. Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France
| | - Marie-Christine Boutron-Ruault
- CESP, Faculté de Médecine - Univ. Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France
| | - Gianluca Severi
- CESP, Faculté de Médecine - Univ. Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France
| | - Theron Johnson
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tilman Kühn
- Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain
| | | | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece; 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece
| | | | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Valeria Pala
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy
| | - Alessio Naccarati
- Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Monique Verschuren
- Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Roel Vermeulen
- Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
| | - Charlotta Rylander
- Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway
| | - Therese Haugdahl Nøst
- Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway
| | - Miguel Rodríguez-Barranco
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - Amaia Molinuevo
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Biodonostia Health Research Institute; Public Health Laboratory in Gipuzkoa, Basque Government, San Sebastian, Spain
| | - María-Dolores Chirlaque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain; Department of Health and Social Sciences, University of Murcia, Murcia, Spain
| | - Eva Ardanaz
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Malin Sund
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Tim Key
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Weimin Ye
- Department of Biobank Research, Umeå University, Umeå, Sweden; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden
| | - Mazda Jenab
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France
| | - Dominique Michaud
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Giuseppe Matullo
- Department Medical Sciences, University of Torino, Italian Institute for Genomic Medicine -IIGM/HuGeF, Torino, Italy
| | - Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Alexandra Nieters
- Center for Chronic Immunodeficiency, Molecular Epidemiology, University Medical Center Freiburg, Freiburg, Germany
| | - Ute Nöthlings
- Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
| | - Suzanne Jeurnink
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Veronique Chajes
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France
| | - Marco Matejcic
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France
| | - Marc Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Antoni Agudo
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain
| | | | - Elisabete Weiderpass
- Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden; Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Bas Bueno-de-Mesquita
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Eric J Duell
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain
| | - Paolo Vineis
- Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Miquel Porta
- Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
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Ahbab S, Ünsal A, Ataoğlu HE, Can TS, Kayaş D, Savaş Y. Prediabetes and Type 2 Diabetes are Independent Risk Factors for Computed Tomography-Estimated Nonalcoholic Fatty Pancreas Disease. Clinics (Sao Paulo) 2019; 74:e1337. [PMID: 31664423 PMCID: PMC6807690 DOI: 10.6061/clinics/2019/e1337] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/26/2019] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES Nonalcoholic fatty pancreas disease (NAFPD) is characterized by excessive fat deposition in the pancreas in the absence of alcohol consumption. In this study, we aimed to detect a possible relationship between adipose tissue accumulation, prediabetes and diabetes. METHODS This cross-sectional and retrospective study included 110 patients. Three groups were classified as controls, patients with prediabetes and patients with type 2 diabetes. The abdominal computed tomography (CT) attenuation measurement results of the pancreas were evaluated independently by two experienced radiologists. CT measurements and biochemical parameters were compared between study groups. The relationship between continuous variables was assessed by using one-way ANOVA. To determine the changes in the dependent variable for the effects on study groups, the independent variable was adjusted using ANCOVA. A p-value less than 0.05 was considered statistically significant. RESULTS The presence of prediabetes and type 2 diabetes was correlated with a decrease in the mean Hounsfield Unit (HU) value of the pancreas (p=0.002). Age was determined to be an independent risk factor and was correlated with NAFPD (p=0.0001). When compared to the controls (p=0.041), 71% of patients with prediabetes and 67% of patients with type 2 diabetes were observed to have an increased incidence of NAFPD. Decreased serum amylase was found to be correlated with the mean HU value of the pancreas (p=0.043). CONCLUSION NAFPD was independently correlated with both prediabetes and type 2 diabetes adjusted for age (p=0.0001) in this study. Additionally, age was determined to be an independent risk factor and was correlated with NAFPD.
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Affiliation(s)
- Süleyman Ahbab
- Internal Medicine Clinic, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
- *Corresponding author. E-mail:
| | - Ahmet Ünsal
- Internal Medicine Clinic, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Hayriye Esra Ataoğlu
- Internal Medicine Clinic, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Tuba Selçuk Can
- Department of Radiology, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Derya Kayaş
- Internal Medicine Clinic, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Yıldıray Savaş
- Department of Radiology, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
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Di Ciaula A, Portincasa P. Diet and Contaminants: Driving the Rise to Obesity Epidemics? Curr Med Chem 2019; 26:3471-3482. [PMID: 28521687 DOI: 10.2174/0929867324666170518095736] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 03/16/2017] [Accepted: 03/16/2017] [Indexed: 02/07/2023]
Abstract
The obesity epidemic is spreading worldwide without reversal trend and despite specific policies oriented to dietary habits and lifestyle, which seem to have modest effects. Genetic factors only partly explain the rise, whereas environmental factors seem to play a key role, mainly by gene-environment interactions through epigenetic mechanisms. A number of animal and human studies point to maternal diet, intestinal microbiota and chemicals introduced as contaminants with food, all factors able to increase the risk of obesity. Widely diffused toxics (mainly BPA, phthalates, pesticides) are able to promote obesity in children and adults, mainly by acting on the differentiation pathway linking multipotent stromal stem cell to mature adipocyte, modulating epigenetic factors and influencing a series of mechanisms finally leading to altered dietary habits, increased adipocyte formation and fat storage. Furthermore, the adipose tissue is an important target for several chemicals (mainly POPs) which represent a threat to metabolic health. In conclusion, besides excessive individual energy intake and inadequate lifestyle, other broadly diffused and modifiable factors (mainly ingestion of toxic chemicals with food) seem to have a critical role in the rapid epidemiological growing of obesity, also considering trans-generational transmission of risk and later development of obesity due to exposure during early life. Further studies are needed, to better assess interactions between cumulative effects of toxic food contaminants and modification of diet and lifestyle, and to verify the efficacy of primary prevention strategies acting on all these factors and potentially able to reverse the continuous rising of the obesity epidemic.
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Affiliation(s)
- Agostino Di Ciaula
- Division of Internal Medicine, Hospital of Bisceglie, Italy - International Society of Doctors for Environment (ISDE), Arezzo, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Medical School, Bari, Italy
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17
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Miao YF, Li J, Zhang YM, Zhu L, Chen H, Yuan L, Hu J, Yi XL, Wu QT, Wan MH, Tang WF. Sheng-jiang powder ameliorates obesity-induced pancreatic inflammatory injury via stimulating activation of the AMPK signalling pathway in rats. World J Gastroenterol 2018; 24:4448-4461. [PMID: 30356974 PMCID: PMC6196332 DOI: 10.3748/wjg.v24.i39.4448] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/12/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the mechanisms by which Sheng-jiang powder (SJP) ameliorates obesity-induced pancreatic inflammatory injury.
METHODS Sprague-Dawley rats were randomized into three groups: normal group (NG), obese group (HLG), or SJP treatment group (HSG). Obesity was induced by feeding a high-fat diet in the HLG and HSG, while the NG received standard chow. Rats were euthanized after 12 wk, and blood and pancreatic tissues were collected for histopathological analyses. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) expression, serum triglyceride and adiponectin levels, and apoptosis in pancreatic acinar cells were assessed. A high-fat AR42J acinar cell injury model was established using very low-density lipoprotein (VLDL). AR42J acinar cell culture supernatant, treated with different interventions, was applied to seven groups of pancreatic stellate cells (PSCs). The proliferation of PSCs and the expression of fibronectin and type I collagenase were assessed.
RESULTS Compared with the NG, we found higher pathological scores for pancreatic tissues, lower serum adiponectin levels, higher expression levels of NF-κB in pancreatic tissues and TGF-β in pancreatic inflammatory cells, and increased apoptosis among pancreatic acinar cells for the HLG (P < 0.05). Compared with the HLG, we found reduced body weight, Lee’s index scores, serum triglyceride levels, and pathological scores for pancreatic tissues; higher serum adiponectin levels; and lower expression levels of NF-κB, in pancreatic tissue and TGF-β in pancreatic inflammatory cells for the HSG (P < 0.05). The in vitro studies showed enhanced PSC activation and increased expression levels of fibronectin and type I collagenase after SJP treatment. An adenosine 5‘-monophosphate-activated protein kinase (AMPK) inhibitor inhibited PSC activation.
CONCLUSION SJP may ameliorate obesity-induced pancreatic inflammatory injury in rats by regulating key molecules of the adiponectin-AMPK signalling pathway.
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Affiliation(s)
- Yi-Fan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Juan Li
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Mei Zhang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ling Yuan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jing Hu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Lin Yi
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Qiu-Ting Wu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mei-Hua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Niu CY, Wu FX. Research status of fatty pancreas. Shijie Huaren Xiaohua Zazhi 2018; 26:1280-1288. [DOI: 10.11569/wcjd.v26.i21.1280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Fatty pancreas is a newly proposed condition which is characterized by fat deposition and steatosis in the pancreas followed by outcome of pancreatic and metabolic complications. It has been found to be correlated with many metabolic disorders and a variety of diseases. Fatty pancreas has been associated with obesity, non-alcoholic fatty liver disease, metabolic syndrome, type 2 diabetes mellitus, acute and chronic pancreatitis, and even pancreatic carcinoma. Therefore, fatty pancreas might not only be an early marker of glucose or lipid metabolism disorders or metabolic syndrome, but also be a predictor of poor outcome of pancreatic related diseases. At present, imaging examination is the main diagnostic method. However, there is currently still a lack of a unified terminology, diagnostic criteria, treatment consensus, and guidelines due to very limited knowledge on this condition. Here we discuss the pathophysiology, pathogenesis, clinical implications, diagnosis, and treatment of fatty pancreas, with an aim to improve the early intervention, treatment, and prognosis prediction of fatty pancreas related metabolic disorders.
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Affiliation(s)
- Chun-Yan Niu
- Department of Gastroenterology, Xiang'an Hospital of Xiamen University, Xiamen 361101, Fujian Province, China,Department of Gastroenterology, the First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, Shaanxi Province, China
| | - Fang-Xiong Wu
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, Shaanxi Province, China
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Di Ciaula A, Garruti G, Wang DQH, Portincasa P. Cholecystectomy and risk of metabolic syndrome. Eur J Intern Med 2018; 53:3-11. [PMID: 29706426 PMCID: PMC8118133 DOI: 10.1016/j.ejim.2018.04.019] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 04/20/2018] [Accepted: 04/21/2018] [Indexed: 02/07/2023]
Abstract
The gallbladder physiologically concentrates and stores bile during fasting and provides rhythmic bile secretion both during fasting and in the postprandial phase to solubilize dietary lipids and fat-soluble vitamins. Bile acids (BAs), major lipid components of bile, play a key role as signaling molecules in modulating gene expression related to cholesterol, BA, glucose and energy metabolism. Cholecystectomy is the most commonly performed surgical procedure worldwide in patients who develop symptoms and/or complications of cholelithiasis of any type. Cholecystectomy per se, however, might cause abnormal metabolic consequences, i.e., alterations in glucose, insulin (and insulin-resistance), lipid and lipoprotein levels, liver steatosis and the metabolic syndrome. Mechanisms are likely mediated by the abnormal transintestinal flow of BAs, producing metabolic signaling that acts without gallbladder rhythmic function and involves the BAs/farnesoid X receptor (FXR) and the BA/G protein-coupled BA receptor 1 (GPBAR-1) axes in the liver, intestine, brown adipose tissue and muscle. Alterations of intestinal microbiota leading to distorted homeostatic processes are also possible. According to this view, cholecystectomy, via BA-induced changes in the enterohepatic circulation, is a risk factor for the metabolic abnormalities and becomes another “fellow traveler” with, or another risk factor for the metabolic syndrome.
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Affiliation(s)
| | - Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari "Aldo Moro" Medical School, Piazza G. Cesare 11, 70124 Bari, Italy
| | - David Q-H Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy.
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20
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Di Ciaula A. Towards 5G communication systems: Are there health implications? Int J Hyg Environ Health 2018; 221:367-375. [PMID: 29402696 DOI: 10.1016/j.ijheh.2018.01.011] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 01/19/2018] [Accepted: 01/20/2018] [Indexed: 02/07/2023]
Abstract
The spread of radiofrequency electromagnetic fields (RF-EMF) is rising and health effects are still under investigation. RF-EMF promote oxidative stress, a condition involved in cancer onset, in several acute and chronic diseases and in vascular homeostasis. Although some evidences are still controversial, the WHO IARC classified RF-EMF as "possible carcinogenic to humans", and more recent studies suggested reproductive, metabolic and neurologic effects of RF-EMF, which are also able to alter bacterial antibiotic resistance. In this evolving scenario, although the biological effects of 5G communication systems are very scarcely investigated, an international action plan for the development of 5G networks has started, with a forthcoming increment in devices and density of small cells, and with the future use of millimeter waves (MMW). Preliminary observations showed that MMW increase skin temperature, alter gene expression, promote cellular proliferation and synthesis of proteins linked with oxidative stress, inflammatory and metabolic processes, could generate ocular damages, affect neuro-muscular dynamics. Further studies are needed to better and independently explore the health effects of RF-EMF in general and of MMW in particular. However, available findings seem sufficient to demonstrate the existence of biomedical effects, to invoke the precautionary principle, to define exposed subjects as potentially vulnerable and to revise existing limits. An adequate knowledge of pathophysiological mechanisms linking RF-EMF exposure to health risk should also be useful in the current clinical practice, in particular in consideration of evidences pointing to extrinsic factors as heavy contributors to cancer risk and to the progressive epidemiological growth of noncommunicable diseases.
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Affiliation(s)
- Agostino Di Ciaula
- Division of Internal Medicine, Hospital of Bisceglie (ASL BAT), Bisceglie, Italy; International Society of Doctors for Environment (ISDE), Arezzo, Italy.
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Abstract
PURPOSE OF REVIEW Gallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease. RECENT FINDINGS Major pathogenetic factors for cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota. Mechanisms of disease are linked with insulin resistance, obesity, the metabolic syndrome, and type 2 diabetes. The role of nuclear receptors, signaling pathways, gut microbiota, and epigenome are being actively investigated. SUMMARY Ongoing research on cholesterol gallstone disease is intensively investigating several pathogenic mechanisms, associated metabolic disorders, new therapeutic approaches, and novel strategies for primary prevention, including lifestyles.
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Affiliation(s)
| | - David Q.-H. Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. Murri”, University of Bari Medical School, Bari, Italy
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22
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Vecchié A, Dallegri F, Carbone F, Bonaventura A, Liberale L, Portincasa P, Frühbeck G, Montecucco F. Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med 2018; 48:6-17. [PMID: 29100895 DOI: 10.1016/j.ejim.2017.10.020] [Citation(s) in RCA: 223] [Impact Index Per Article: 31.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 10/24/2017] [Accepted: 10/26/2017] [Indexed: 12/15/2022]
Abstract
The pro-inflammatory state of the visceral adipose tissue (VAT) is supposed to accelerate cardiovascular (CV) and metabolic diseases in obese subjects. Some studies have recently reported an improved CV prognosis in certain obese and overweight patients as compared with leaner ones. This phenomenon, known as the "obesity paradox" (OP), has been described in many chronic diseases. This narrative review is based on the material searched for and obtained via PubMed and Web of Science up to May 2017. The search terms we used were: "obesity, paradox, adipose tissue" in combination with "cardiovascular, coronary heart disease, heart failure, arrhythmias". Using the current Body Mass Index (BMI)-based obesity definition, individuals with different clinical and biochemical characteristics are gathered together in the same category. Emerging evidence point to the existence of many "Obesity phenotypes" with different association with CV risk, accordingly to physical and life-style features. In this narrative review, we discussed if obesity phenotypes may be associated with a different CV risk, potentially explaining the OP. As a globally accepted definition of obesity is still lacking, we emphasized the need of a new approach, which should consider the heterogeneity of obesity. Better defining "obesities" and related CV risk is critical to markedly improve the classical BMI-based definition of obesity.
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Affiliation(s)
- Alessandra Vecchié
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Franco Dallegri
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia, 10 Largo Benzi, 16132 Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Centre for Molecular Cardiology, University of Zürich, 12 Wagistrasse, 8952 Schlieren, Switzerland
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Medical School, Bari, Italy
| | - Gema Frühbeck
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia, 10 Largo Benzi, 16132 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy.
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Garruti G, Wang DQH, Di Ciaula A, Portincasa P. Cholecystectomy: a way forward and back to metabolic syndrome? J Transl Med 2018; 98:4-6. [PMID: 29297503 PMCID: PMC8114797 DOI: 10.1038/labinvest.2017.129] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The gallbladder provides rhythmic secretion of concentrated bile acids (BAs) during fasting and postprandially contributes to digestion of dietary lipids. In addition, BAs activate metabolic pathways governing gluco-lipid homeostasis and energy expenditure via the farnesoid X nuclear receptor (FXR), G protein-coupled BA receptor 1 (GPBAR-1), and fibroblast growth factor 19 (FGF19) in the liver, intestine, brown fat, and muscle. Cholecystectomy is standard treatment worldwide for symptomatic gallstone patients. As excellently reviewed by Chen et al, cholecystectomy may disrupt enterohepatic recycling of, and signaling by, BAs. Further studies are needed to investigate whether gallbladder removal is an independent risk factor for development of the metabolic syndrome.
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Affiliation(s)
- Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari 'Aldo Moro' Medical School, Bari, Italy
| | - David Q-H Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | | | - Piero Portincasa
- Clinica Medica 'A Murri', Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
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Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence. BIOMED RESEARCH INTERNATIONAL 2017; 2017:1981837. [PMID: 29349066 PMCID: PMC5733953 DOI: 10.1155/2017/1981837] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Accepted: 10/31/2017] [Indexed: 12/11/2022]
Abstract
Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.
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25
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Garruti G, Di Ciaula A, Wang HH, Wang DQH, Portincasa P. Cross-Talk Between Bile Acids and Gastro-Intestinal and Thermogenic Hormones: Clues from Bariatric Surgery. Ann Hepatol 2017; 16:s68-s82. [PMID: 29080342 DOI: 10.5604/01.3001.0010.5499] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 09/06/2017] [Indexed: 02/05/2023]
Abstract
Obesity is rapidly increasing and has reached epidemic features worldwide. It´s linked to insulin resistance, systemic low-grade inflammation and common pathogenic pathways with a number of comorbidities (including cancer), leading to high mortality rates. Besides change of lifestyles (diet and physical exercise) and pharmacological therapy, bariatric surgery is able to rapidly improve several metabolic and morphologic features associated with excessive fat storage, and currently represents an in vivo model to study the pathogenic mechanisms underlying obesity and obesity-related complications. Studies on obese subjects undergoing bariatric surgery find that the effects of surgery are not simply secondary to gastric mechanical restriction and malabsorption which induce body weight loss. In fact, some surgical procedures positively modify key pathways involving the intestine, bile acids, receptor signaling, gut microbiota, hormones and thermogenesis, leading to systemic metabolic changes. Furthermore, bariatric surgery represents a suitable model to evaluate the gene-environment interaction and some epigenetic mechanisms linking obesity and insulin resistance to metabolic diseases.
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Affiliation(s)
- Gabriella Garruti
- Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy
| | | | - Helen H Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - David Q-H Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy
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26
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Khoury T, Asombang AW, Berzin TM, Cohen J, Pleskow DK, Mizrahi M. The Clinical Implications of Fatty Pancreas: A Concise Review. Dig Dis Sci 2017; 62:2658-2667. [PMID: 28791556 DOI: 10.1007/s10620-017-4700-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 07/27/2017] [Indexed: 12/19/2022]
Abstract
Fatty pancreas is a newly recognized condition which is poorly investigated until today as compared to nonalcoholic fatty liver disease. It is characterized by pancreatic fat accumulation and subsequent development of pancreatic and metabolic complications. Association of fatty pancreas have been described with type 2 diabetes mellitus, acute and chronic pancreatitis and even pancreatic carcinoma. In this review article, we provide an update on clinical implications, pathogenesis, diagnosis, treatment and outcomes.
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Affiliation(s)
- Tawfik Khoury
- Department of Internal Medicine, Department of Gastroenterology and Liver Unit, Hadassah Hebrew University Medical Center, Ein Kerem, P.O.B. 12000, 91120, Jerusalem, Israel.
| | - Akwi W Asombang
- Division of Gastroenterology, Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, 02215, USA
| | - Tyler M Berzin
- Division of Gastroenterology, Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, 02215, USA
| | - Jonah Cohen
- Center of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Dana 501, Boston, MA, 02215, USA
| | - Douglas K Pleskow
- Division of Gastroenterology, Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, 02215, USA
| | - Meir Mizrahi
- Division of Gastroenterology, Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, 02215, USA
- Division of Gastroenterology, Center for Advanced Endoscopy, University of South Alabama, Mobile, AL, USA
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Alempijevic T, Dragasevic S, Zec S, Popovic D, Milosavljevic T. Non-alcoholic fatty pancreas disease. Postgrad Med J 2017; 93:226-230. [PMID: 28069746 DOI: 10.1136/postgradmedj-2016-134546] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 12/18/2016] [Indexed: 02/07/2023]
Abstract
Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity. It appears to arise as obesity progresses and after an initial phase of pancreatic hypertrophy and hyperplasia, fatty infiltration becomes apparent. Various studies have demonstrated that NAFPD may exacerbate the severity of acute pancreatitis, promote pancreatic dysfunction associated with insulin resistance and T2DM, and even have links to the development of pancreatic carcinoma, and therefore, it must be investigated in further detail.
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Affiliation(s)
- Tamara Alempijevic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Sanja Dragasevic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
| | - Simon Zec
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Dragan Popovic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Tomica Milosavljevic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
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28
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Catanzaro R, Cuffari B, Italia A, Marotta F. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease. World J Gastroenterol 2016; 22:7660-7675. [PMID: 27678349 PMCID: PMC5016366 DOI: 10.3748/wjg.v22.i34.7660] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Revised: 07/25/2016] [Accepted: 08/10/2016] [Indexed: 02/06/2023] Open
Abstract
After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.
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29
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Portincasa P, Di Ciaula A, Grattagliano I. Preventing a Mass Disease: The Case of Gallstones Disease: Role and Competence for Family Physicians. Korean J Fam Med 2016; 37:205-213. [PMID: 27468338 PMCID: PMC4961852 DOI: 10.4082/kjfm.2016.37.4.205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 04/22/2016] [Accepted: 04/25/2016] [Indexed: 02/05/2023] Open
Abstract
Gallstone formation is the result of a complex interaction between genetic and nongenetic factors. We searched and reviewed the available literature to define how the primary prevention of gallstones (cholesterol gallstones in particular) could be applied in general practice. Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case-controlled studies were analyzed and graded for evidence quality. The epidemiological data confirmed that genetic factors are estimated to account for only approximately 25% of the overall risk of gallstones, while metabolic/environmental factors are at least partially modifiable in stone-free risk groups, and are thus modifiable by primary prevention measures related to diet, lifestyle, and environmental factors (i.e., rapid weight loss, bariatric surgery, somatostatin or analogues therapy, transient gallbladder stasis, and hormone therapy). There is no specific recommendation for the secondary prevention of recurrent gallstones. Family physicians can contribute to preventing gallstones due to their capability to identify and effectively manage several risk factors discussed in this study. Although further studies are needed to better elucidate the involvement of epigenetic factors that may regulate the effect of environment and lifestyle on gene expression in the primary prevention of gallstone formation, preventive interventions are feasible and advisable in the general practice setting.
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Affiliation(s)
- Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy
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30
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Zhang YP, Zhang YY, Duan DD. From Genome-Wide Association Study to Phenome-Wide Association Study: New Paradigms in Obesity Research. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2016; 140:185-231. [PMID: 27288830 DOI: 10.1016/bs.pmbts.2016.02.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Obesity is a condition in which excess body fat has accumulated over an extent that increases the risk of many chronic diseases. The current clinical classification of obesity is based on measurement of body mass index (BMI), waist-hip ratio, and body fat percentage. However, these measurements do not account for the wide individual variations in fat distribution, degree of fatness or health risks, and genetic variants identified in the genome-wide association studies (GWAS). In this review, we will address this important issue with the introduction of phenome, phenomics, and phenome-wide association study (PheWAS). We will discuss the new paradigm shift from GWAS to PheWAS in obesity research. In the era of precision medicine, phenomics and PheWAS provide the required approaches to better definition and classification of obesity according to the association of obese phenome with their unique molecular makeup, lifestyle, and environmental impact.
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Affiliation(s)
- Y-P Zhang
- Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Y-Y Zhang
- Department of Cardiology, Changzhou Second People's Hospital, Changzhou, Jiangsu, China
| | - D D Duan
- Laboratory of Cardiovascular Phenomics, Center for Cardiovascular Research, Department of Pharmacology, and Center for Molecular Medicine, University of Nevada School of Medicine, Reno, NV, United States.
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31
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Mughetti M, Calculli L, Chiesa AM, Ciccarese F, Rrusho O, Pezzilli R. Implications and issues related to familial pancreatic cancer: a cohort study of hospitalized patients. BMC Gastroenterol 2016; 16:6. [PMID: 26767414 PMCID: PMC4714470 DOI: 10.1186/s12876-016-0421-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Background The surveillance of subjects at risk of pancreatic cancer is restricted to clinical research; the incidence of familial pancreatic cancer needs to be better established. Thus, we aimed to evaluate the frequency of familial pancreatic cancer in a population of hospitalized patients with pancreatic cancer. Methods A retrospective study based on the hospital charts of patients discharged with a diagnosis of pancreatic cancer. One hundred and eighty-seven patients or their relatives were called for a phone interview. Results There were 97 males (51.9 %) and 90 (48.1 %) females. The overall mean ± SD age was 67.3 ± 11.8 years; the age of males was similar to that of females (P = 0140). The mean size of the tumors found was 36.3 ± 17.4 mm (range of 5–110 mm); it was related to gender but was not related to the site of the tumor or the age of the patient. Regarding genetic diseases, three females (1.6 %) had familial adenomatous polyposis; three patients (1 male and two females) (1.6 %) had at least one relative with pancreatic cancer whereas only one 80-year old male patient (0.5 %) had two relatives affected by pancreatic cancer (the mother had died at the 65 years of age and the brother had died at 75 years of age). Conclusions The frequency of familial pancreatic ductal adenocarcinoma is small, but its importance, from the point of view of early diagnosis, is not negligible and patients with a risk of familial cancer merit an appropriate clinical follow-up.
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Affiliation(s)
- Martina Mughetti
- Department of Diagnostic and Preventive Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy
| | - Lucia Calculli
- Department of Diagnostic and Preventive Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy
| | - Anna Maria Chiesa
- Department of Diagnostic and Preventive Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy
| | - Federica Ciccarese
- Department of Diagnostic and Preventive Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy
| | - Odeta Rrusho
- Department of Diagnostic and Preventive Medicine, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy
| | - Raffaele Pezzilli
- Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy.
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Portincasa P, Di Ciaula A, de Bari O, Garruti G, Palmieri VO, Wang DQH. Management of gallstones and its related complications. Expert Rev Gastroenterol Hepatol 2015; 10:93-112. [PMID: 26560258 DOI: 10.1586/17474124.2016.1109445] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications.
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Affiliation(s)
- P Portincasa
- a Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
| | - A Di Ciaula
- b Division of Internal Medicine , Hospital of Bisceglie , Bisceglie , Italy
| | - O de Bari
- a Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
- d Department of Internal Medicine, Division of Gastroenterology and Hepatology , Saint Louis University School of Medicine , St. Louis , MO , USA
| | - G Garruti
- c Department of Emergency and Organ Transplants, Section of Endocrinology, Andrology and Metabolic Diseases , University of Bari Medical School , Bari , Italy
| | - V O Palmieri
- a Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
| | - D Q-H Wang
- d Department of Internal Medicine, Division of Gastroenterology and Hepatology , Saint Louis University School of Medicine , St. Louis , MO , USA
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Possible role of vitamin D3 on the adipocyte/fibroblast trans-differentiation mediated by pancreas cancer. CURRENT HEALTH SCIENCES JOURNAL 2015; 41:5-10. [PMID: 30151244 PMCID: PMC6057533 DOI: 10.12865/chsj.41.01.01] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 03/15/2015] [Indexed: 12/15/2022]
Abstract
In pancreatic tumors, white adipose tissue and metabolic disorders related to
adipocytes, are recently reviewed as important co-factors in pancreas pathology.
Cell differentiation in pancreatic cancer might involve therefore adipose tissue
and factors released by adipocytes should play a fundamental role both in cancer
onset and in its progression. Among these molecules, a great interest has been
devoted quite recently to the hormonal role exerted by vitamin D3 in pancreatic
cancer, particularly its active 1,25 dihydroxylated form. Despite the wide bulk
of evidence reporting the chemopreventive role of vitamin D, the mechanism by
which active vitamin D3 is able to counteract cancer progression and malignancy
is yet far to be elucidated.
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