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Lecoutre S, Rebière C, Maqdasy S, Lambert M, Dussaud S, Abatan JB, Dugail I, Gautier EL, Clément K, Marcelin G. Enhancing adipose tissue plasticity: progenitor cell roles in metabolic health. Nat Rev Endocrinol 2025; 21:272-288. [PMID: 39757324 DOI: 10.1038/s41574-024-01071-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/27/2024] [Indexed: 01/07/2025]
Abstract
Adipose tissue demonstrates considerable plasticity and heterogeneity, enabling metabolic, cellular and structural adaptations to environmental signals. This adaptability is key for maintaining metabolic homeostasis. Impaired adipose tissue plasticity can lead to abnormal adipose tissue responses to metabolic cues, which contributes to the development of cardiometabolic diseases. In chronic obesity, white adipose tissue undergoes pathological remodelling marked by adipocyte hypertrophy, chronic inflammation and fibrosis, which are linked to local and systemic insulin resistance. Research data suggest that the capacity for healthy or unhealthy white adipose tissue remodelling might depend on the intrinsic diversity of adipose progenitor cells (APCs), which sense and respond to metabolic cues. This Review highlights studies on APCs as key determinants of adipose tissue plasticity, discussing differences between subcutaneous and visceral adipose tissue depots during development, growth and obesity. Modulating APC functions could improve strategies for treating adipose tissue dysfunction and metabolic diseases in obesity.
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Affiliation(s)
- Simon Lecoutre
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France.
| | - Clémentine Rebière
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Salwan Maqdasy
- Department of Medicine, Karolinska Institutet Hospital, Stockholm, Sweden
| | - Mélanie Lambert
- Institut National de la Santé et de la Recherche Médicale, Bobigny, France
- Labex Inflamex, Université Sorbonne Paris Nord, Alliance Sorbonne Paris Cité, Bobigny, France
| | - Sébastien Dussaud
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Jimon Boniface Abatan
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Isabelle Dugail
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Emmanuel L Gautier
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Karine Clément
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France.
- Department of Nutrition, Pitie-Salpêtriere Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
| | - Geneviève Marcelin
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France.
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2
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Gamal M, Awad MA, Shadidizaji A, Ibrahim MA, Ghoneim MA, Warda M. In vivo and in silico insights into the antidiabetic efficacy of EVOO and hydroxytyrosol in a rat model. J Nutr Biochem 2025; 135:109775. [PMID: 39370013 DOI: 10.1016/j.jnutbio.2024.109775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/26/2024] [Accepted: 09/28/2024] [Indexed: 10/08/2024]
Abstract
Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol Hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and Hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an 8-week treatment with either EVOO (90 g/kg of the diet) (DO) or Hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired β-cell function. In contrast, treatments with EVOO and Hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, Hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced β-cell survival. Molecular docking and dynamics confirm Hydroxytyrosol's high affinity binding to PGC-1α, IRE-1α, and PPAR-γ, particularly IRE-1α, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and Hydroxytyrosol. Moreover, the favorable docking scores of Hydroxytyrosol with PGC-1α, IRE-1α, and PPAR-γ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.
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Affiliation(s)
- Mahmoud Gamal
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States
| | - Mohamed A Awad
- Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Azizeh Shadidizaji
- Department of Plant Biotechnology, Faculty of Agriculture, Ataturk University, Erzurum, Turkey
| | - Marwa A Ibrahim
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Magdy A Ghoneim
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
| | - Mohamad Warda
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey
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Calderón-DuPont D, Torre-Villalvazo I, Díaz-Villaseñor A. Is insulin resistance tissue-dependent and substrate-specific? The role of white adipose tissue and skeletal muscle. Biochimie 2023; 204:48-68. [PMID: 36099940 DOI: 10.1016/j.biochi.2022.08.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 08/19/2022] [Accepted: 08/31/2022] [Indexed: 01/12/2023]
Abstract
Insulin resistance (IR) refers to a reduction in the ability of insulin to exert its metabolic effects in organs such as adipose tissue (AT) and skeletal muscle (SM), leading to chronic diseases such as type 2 diabetes, hepatic steatosis, and cardiovascular diseases. Obesity is the main cause of IR, however not all subjects with obesity develop clinical insulin resistance, and not all clinically insulin-resistant people have obesity. Recent evidence implies that IR onset is tissue-dependent (AT or SM) and/or substrate-specific (glucometabolic or lipometabolic). Therefore, the aims of the present review are 1) to describe the glucometabolic and lipometabolic activities of insulin in AT and SM in the maintenance of whole-body metabolic homeostasis, 2) to discuss the pathophysiology of substrate-specific IR in AT and SM, and 3) to highlight novel validated tests to assess tissue and substrate-specific IR that are easy to perform in clinical practice. In AT, glucometabolic IR reduces glucose availability for glycerol and fatty acid synthesis, thus decreasing the esterification and synthesis of signaling bioactive lipids. Lipometabolic IR in AT impairs the antilipolytic effect of insulin and lipogenesis, leading to an increase in circulating FFAs and generating lipotoxicity in peripheral tissues. In SM, glucometabolic IR reduces glucose uptake, whereas lipometabolic IR impairs mitochondrial lipid oxidation, increasing oxidative stress and inflammation, all of which lead to metabolic inflexibility. Understanding tissue-dependent and substrate-specific IR is of paramount importance for early detection before clinical manifestations and for the development of more specific treatments or direct interventions to prevent chronic life-threatening diseases.
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Affiliation(s)
- Diana Calderón-DuPont
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico; Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico
| | - Ivan Torre-Villalvazo
- Departamento de Fisiología de la Nutrición, Instituto Nacional en Ciencias Médicas y Nutricíon Salvador Zubirán, Mexico City, 14000, Mexico
| | - Andrea Díaz-Villaseñor
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico.
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Zhang Z, Wang J, Lin Y, Chen J, Liu J, Zhang X. Nutritional activities of luteolin in obesity and associated metabolic diseases: an eye on adipose tissues. Crit Rev Food Sci Nutr 2022; 64:4016-4030. [PMID: 36300856 DOI: 10.1080/10408398.2022.2138257] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Obesity is characterized by excessive body fat accumulation and is a high-risk factor for metabolic comorbidities, including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. In lean individuals, adipose tissue (AT) is not only an important regulatory organ for energy storage and metabolism, but also an indispensable immune and endocrine organ. The sustained energy imbalance induces adipocyte hypotrophy and hyperplasia as well as AT remodeling, accompanied by chronic low-grade inflammation and adipocytes dysfunction in AT, ultimately leading to systemic insulin resistance and ectopic lipid deposition. Luteolin is a natural flavonoid widely distributed in fruits and vegetables and possesses multifold biological activities, such as antioxidant, anticancer, and anti-inflammatory activities. Diet supplementation of this flavonoid has been reported to inhibit AT lipogenesis and inflammation as well as the ectopic lipid deposition, increase AT thermogenesis and systemic energy expenditure, and finally improve obesity and associated metabolic diseases. The purpose of this review is to reveal the nutritional activities of luteolin in obesity and its complications with emphasis on its action on AT energy metabolism, immunoregulation, and endocrine intervention.
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Affiliation(s)
- Zhixin Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Jiahui Wang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Yan Lin
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Juan Chen
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Jian Liu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
- Engineering Research Center of Bioprocess, Ministry of Education, Hefei University of Technology, Hefei, Anhui, China
| | - Xian Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
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5
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Lecoutre S, Lambert M, Drygalski K, Dugail I, Maqdasy S, Hautefeuille M, Clément K. Importance of the Microenvironment and Mechanosensing in Adipose Tissue Biology. Cells 2022; 11:cells11152310. [PMID: 35954152 PMCID: PMC9367348 DOI: 10.3390/cells11152310] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/19/2022] [Accepted: 07/23/2022] [Indexed: 11/16/2022] Open
Abstract
The expansion of adipose tissue is an adaptive mechanism that increases nutrient buffering capacity in response to an overall positive energy balance. Over the course of expansion, the adipose microenvironment undergoes continual remodeling to maintain its structural and functional integrity. However, in the long run, adipose tissue remodeling, typically characterized by adipocyte hypertrophy, immune cells infiltration, fibrosis and changes in vascular architecture, generates mechanical stress on adipose cells. This mechanical stimulus is then transduced into a biochemical signal that alters adipose function through mechanotransduction. In this review, we describe the physical changes occurring during adipose tissue remodeling, and how they regulate adipose cell physiology and promote obesity-associated dysfunction in adipose tissue.
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Affiliation(s)
- Simon Lecoutre
- Nutrition and Obesities: Systemic Approaches Research Group (Nutri-Omics), Sorbonne Université, INSERM, F-75013 Paris, France; (S.L.); (K.D.); (I.D.)
| | - Mélanie Lambert
- Labex Inflamex, Université Sorbonne Paris Nord, INSERM, F-93000 Bobigny, France;
| | - Krzysztof Drygalski
- Nutrition and Obesities: Systemic Approaches Research Group (Nutri-Omics), Sorbonne Université, INSERM, F-75013 Paris, France; (S.L.); (K.D.); (I.D.)
| | - Isabelle Dugail
- Nutrition and Obesities: Systemic Approaches Research Group (Nutri-Omics), Sorbonne Université, INSERM, F-75013 Paris, France; (S.L.); (K.D.); (I.D.)
| | - Salwan Maqdasy
- Department of Medicine (H7), Karolinska Institutet Hospital, C2-94, 14186 Stockholm, Sweden;
| | - Mathieu Hautefeuille
- Laboratoire de Biologie du Développement (UMR 7622), IBPS, Sorbonne Université, F-75005 Paris, France;
| | - Karine Clément
- Nutrition and Obesities: Systemic Approaches Research Group (Nutri-Omics), Sorbonne Université, INSERM, F-75013 Paris, France; (S.L.); (K.D.); (I.D.)
- Assistance Publique Hôpitaux de Paris, Nutrition Department, CRNH Ile-de-France, Pitié-Salpêtrière Hospital, F-75013 Paris, France
- Correspondence: or
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6
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Yanina IY, Tanikawa Y, Genina EA, Dyachenko PA, Tuchina DK, Bashkatov AN, Dolotov LE, Tarakanchikova YV, Terentuk GS, Navolokin NA, Bucharskaya AB, Maslyakova GN, Iga Y, Takimoto S, Tuchin VV. Immersion optical clearing of adipose tissue in rats: ex vivo and in vivo studies. JOURNAL OF BIOPHOTONICS 2022; 15:e202100393. [PMID: 35340116 DOI: 10.1002/jbio.202100393] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 06/14/2023]
Abstract
Optical clearing (OC) of adipose tissue has not been studied enough, although it can be promising in medical applications, including surgery and cosmetology, for example, to visualize blood vessels or increase the permeability of tissues to laser beams. The main objective of this work is to develop technology for OC of abdominal adipose tissue in vivo using hyperosmotic optical clearing agents (OCAs). The maximum OC effect (77%) was observed for ex vivo rat adipose tissue samples exposed to OCA on fructose basis for 90 minutes. For in vivo studies, the maximum effect of OC (65%) was observed when using OCA based on diatrizoic acid and dimethylsulfoxide for 120 minutes. Histological analysis showed that in vivo application of OCAs may induce a limited local necrosis of fat cells. The efficiency of OC correlated with local tissue damage through cell necrosis due to accompanied cell lipolysis.
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Affiliation(s)
- Irina Yu Yanina
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | | | - Elina A Genina
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Polina A Dyachenko
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Daria K Tuchina
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Alexey N Bashkatov
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Leonid E Dolotov
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
| | | | | | - Nikita A Navolokin
- Science Medical Center, Saratov State University, Saratov, Russia
- Research-Scientific Institute of Fundamental and Clinic Uronephrology, Saratov State Medical University, Saratov, Russia
| | - Alla B Bucharskaya
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
- Science Medical Center, Saratov State University, Saratov, Russia
- Research-Scientific Institute of Fundamental and Clinic Uronephrology, Saratov State Medical University, Saratov, Russia
| | - Galina N Maslyakova
- Science Medical Center, Saratov State University, Saratov, Russia
- Research-Scientific Institute of Fundamental and Clinic Uronephrology, Saratov State Medical University, Saratov, Russia
| | | | | | - Valery V Tuchin
- Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
- Science Medical Center, Saratov State University, Saratov, Russia
- Laboratory of Laser Diagnostics of Technical and Living Systems, Institute of Precision Mechanics and Control, FRC "Saratov Scientific Centre of the Russian Academy of Sciences", Saratov, Russia
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7
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Busetto L, Sbraccia P, Vettor R. Obesity management: at the forefront against disease stigma and therapeutic inertia. Eat Weight Disord 2022; 27:761-768. [PMID: 34052990 PMCID: PMC8933346 DOI: 10.1007/s40519-021-01217-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/17/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence.
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Affiliation(s)
- Luca Busetto
- Department of Medicine, University of Padova, Padua, Italy.
- Clinica Medica 3, Azienda Ospedale-Università di Padova, Via Giustiniani 2, 35128, Padua, Italy.
| | - Paolo Sbraccia
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Roberto Vettor
- Department of Medicine, University of Padova, Padua, Italy
- Clinica Medica 3, Azienda Ospedale-Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
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Maqdasy S, Lecoutre S, Renzi G, Frendo-Cumbo S, Rizo-Roca D, Moritz T, Juvany M, Hodek O, Gao H, Couchet M, Witting M, Kerr A, Bergo MO, Choudhury RP, Aouadi M, Zierath JR, Krook A, Mejhert N, Rydén M. Impaired phosphocreatine metabolism in white adipocytes promotes inflammation. Nat Metab 2022; 4:190-202. [PMID: 35165448 PMCID: PMC8885409 DOI: 10.1038/s42255-022-00525-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 01/05/2022] [Indexed: 02/07/2023]
Abstract
The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.
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Grants
- SM was supported by the Université Clermont Auvergne, Société Francophone du Diabète and Fondation Bettencourt Schueller.
- S.F.C. is supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet.
- the NovoNordisk Foundation (NNF20OC0061149), CIMED, Swedish Research Council.
- Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
- Margareta af Uggla’s foundation, the Swedish Research Council, ERC-SyG SPHERES (856404 to M.R.), the NovoNordisk Foundation (including the Tripartite Immuno-metabolism Consortium Grant Number NNF15CC0018486, the MSAM consortium NNF15SA0018346 and the MeRIAD consortium Grant number 0064142), Knut and Alice Wallenbergs Foundation, CIMED, the Swedish Diabetes Foundation, the Stockholm County Council and the Strategic Research Program in Diabetes at Karolinska Institutet.
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Affiliation(s)
- Salwan Maqdasy
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
- CHU Clermont-Ferrand, Service d'endocrinologie, diabétologie et maladies métaboliques, Clermont-Ferrand, France
- Laboratoire GReD, Université Clermont Auvergne, Faculté de Médecine, Clermont Ferrand, France
| | - Simon Lecoutre
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
| | - Gianluca Renzi
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
| | - Scott Frendo-Cumbo
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
| | - David Rizo-Roca
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Moritz
- Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden
- The NovoNordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marta Juvany
- Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden
| | - Ondrej Hodek
- Swedish Metabolomics Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden
| | - Hui Gao
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Morgane Couchet
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
| | - Michael Witting
- Metabolomics and proteomics core (MPC), Helmholtz Zentrum München, Neuherberg, Germany
- Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, Neuherberg, Germany
- Chair of Analytical Food Chemistry, TUM School of Life Sciences, Freising, Germany
| | - Alastair Kerr
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
| | - Martin O Bergo
- Department of Biosciences and Nutrition, Karolinska Comprehensive Cancer Center, Karolinska Institutet, Huddinge, Sweden
| | | | - Myriam Aouadi
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden
| | - Juleen R Zierath
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Anna Krook
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Niklas Mejhert
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.
| | - Mikael Rydén
- Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.
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9
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Lecoutre S, Maqdasy S, Breton C. Maternal obesity as a risk factor for developing diabetes in offspring: An epigenetic point of view. World J Diabetes 2021; 12:366-382. [PMID: 33889285 PMCID: PMC8040079 DOI: 10.4239/wjd.v12.i4.366] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 01/30/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023] Open
Abstract
According to the developmental origin of health and disease concept, the risk of many age-related diseases is not only determined by genetic and adult lifestyle factors but also by factors acting during early development. In particular, maternal obesity and neonatal accelerated growth predispose offspring to overweight and type 2 diabetes (T2D) in adulthood. This concept mainly relies on the developmental plasticity of adipose tissue and pancreatic β-cell programming in response to suboptimal milieu during the perinatal period. These changes result in unhealthy hypertrophic adipocytes with decreased capacity to store fat, low-grade inflammation and loss of insulin-producing pancreatic β-cells. Over the past years, many efforts have been made to understand how maternal obesity induces long-lasting adipose tissue and pancreatic β-cell dysfunction in offspring and what are the molecular basis of the transgenerational inheritance of T2D. In particular, rodent studies have shed light on the role of epigenetic mechanisms in linking maternal nutritional manipulations to the risk for T2D in adulthood. In this review, we discuss epigenetic adipocyte and β-cell remodeling during development in the progeny of obese mothers and the persistence of these marks as a basis of obesity and T2D predisposition.
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Affiliation(s)
- Simon Lecoutre
- Department of Medicine (H7), Karolinska Institutet, Stockholm 141-86, Sweden
- University of Lille, EA4489, Maternal Malnutrition and Programming of Metabolic Diseases, Lille 59000, France
| | - Salwan Maqdasy
- Department of Medicine (H7), Karolinska Institutet, Stockholm 141-86, Sweden
- Clermont-Ferrand CHU, Department of Endocrinology, Diabetology and Metabolic Diseases, Clermont-Ferrand 63003, France
| | - Christophe Breton
- University of Lille, EA4489, Maternal Malnutrition and Programming of Metabolic Diseases, Lille 59000, France
- U1283-UMR8199-EGID, University of Lille, Institut National de la Santé Et de la Recherche Médicale, Centre National de la Recherche Scientifique, Lille 59000, France
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