• bmi
• gerd
• masld
• obesity
• risk factor

• Adipose regeneration
• Decellularized adipose-derived matrix
• Fiber
• Structure

• Biological sciences
• Developmental neuroscience
• Neuroscience
• Physiology

• F30 AA027698 NIAAA NIH HHS
• R01 AA026756 NIAAA NIH HHS

• Adipose tissue
• Hepatic steatosis
• Insulin resistance
• Obesity
• Pancreas
• Peroxisome proliferator-activated receptors

• Humans
• Peroxisome Proliferator-Activated Receptors/agonists
• Peroxisome Proliferator-Activated Receptors/metabolism
• Insulin Resistance/physiology
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• COVID-19/metabolism
• Adipose Tissue/metabolism
• Obesity/metabolism
• Metabolic Diseases
• Pancreas/metabolism
• Fatty Liver/metabolism

In recent years, more studies have observed that patients with Prader–Willi syndrome have lower insulin levels and lower insulin resistance than body mass index-matched controls, which may suggest protected glucose metabolism.

The PubMed and Web of Science online databases were searched to identify relevant studies published in the English language using the terms “Prader–Willi syndrome” with “glucose”, “insulin”, “diabetes mellitus”, “fat”, “adipo*”, “ghrelin”, “oxytocin”, “irisin” or “autonomic nervous system”.

The prevalence of impaired glucose intolerance, type 2 diabetes mellitus and some other obesity-associated complications in patients with Prader–Willi syndrome tends to be lower when compared to that in general obesity, which is consistent with the hypothetically protected glucose metabolism. Factors including adipose tissue, adiponectin, ghrelin, oxytocin, irisin, growth hormone and the autonomic nervous system possibly modulate insulin sensitivity in patients with Prader–Willi syndrome.

Although lower insulin levels, lower IR and protected glucose metabolism are widely reported in PWS patients, the causes are still mysterious. Based on existing knowledge, we cannot determine which factor is of utmost importance and what are the underlying mechanisms, and further research is in urgent need.

• Adipose
• Hormones
• Insulin
• Insulin resistance
• Prader–Willi syndrome

• adipocyte
• autonomic nervous system
• hypothalamic obesity
• splenectomy
• vagotomy

• BMI
• hypothalamic obesity
• metformin
• weight gain

Adipose tissue is the primary energy reservoir of the human body, which also possesses endocrine functions. The glucagon‐like peptide agonist liraglutide produces weight loss, although the specific effects on adipose tissue are unknown. We aimed to characterize the white adipose tissue composition and pericellular fibrosis of subcutaneous adipose tissue in response to liraglutide treatment. Furthermore, we explored the level of circulating free fatty acids, cluster of differentiation 163 (CD163) macrophage marker, leptin and adiponectin. Thirty‐nine adults with type 1 diabetes and polyneuropathy were randomly assigned to 26 weeks of liraglutide or placebo treatment. Biopsies of subcutaneous tissue were formalin‐fixed stained with picrosirius red to visualize collagen or immunohistochemically stained for CD163. Serum concentrations of free fatty acids, CD163, leptin and adiponectin were assessed with immunoassays or multiplex panels. In comparison with placebo, liraglutide induced weight loss (3.38 kg, 95% CI −5.29; −1.48, P < 0.001), but did not cause any differences in cell size, distribution of CD163‐positive cells, pericellular fibrosis and serum levels of free fatty acids, CD163, leptin or adiponectin (all P < 0.1). Additionally, no associations between weight loss, cell size and serum markers were found (all P > 0.08). In conclusion, despite liraglutide's effect on weight loss, sustained alterations in subcutaneous adipose tissue did not seem to appear.

• adipose
• anti-inflammatory drugs
• diabetes mellitus
• liraglutide
• weight loss drugs

• Animals
• Circadian Rhythm/physiology
• Humans
• Light/adverse effects
• Mice
• Obesity/physiopathology
• Rats

• Universiteit van Amsterdam

• ILC1
• TH2
• neuro-inflammation
• obesity
• pain
• white adipose tissue

• Ectopic fat
• Glucagon-like peptide-1 receptor agonist
• Hepatic steatosis
• Liraglutide
• Myocardial steatosis
• Non-alcoholic fatty liver disease
• Type 2 diabetes mellitus

• Aged
• Anthropometry
• Diabetes Mellitus, Type 2/drug therapy
• Double-Blind Method
• Female
• Humans
• Lipid Metabolism/drug effects
• Liraglutide/therapeutic use
• Liver/metabolism
• Male
• Middle Aged
• Myocardium/metabolism
• Placebo Effect
• Subcutaneous Fat/metabolism
• Triglycerides/metabolism

• Novo Nordisk

Olanzapine is one of the atypical antipsychotics widely used in the treatment of schizophrenia and has been associated with metabolic changes as adverse effects, including hyperglycemia, dyslipidemia, and weight gain. In a batch of adult female Wistar rats, we studied the prolonged-release intramuscular olanzapine pamoate induced quantitative changes of visceral and subcutaneous adipose tissue. We also assessed the effects of the combinations of olanzapine pamoate with melatonin, metformin, and melatonin plus metformin, administered by gastric gavage. A higher mean weight of the visceral and subcutaneous adipose tissue per animal was noted in the olanzapine pamoate exposed group compared to controls. The association with melatonin, metformin, or the combination of melatonin with metformin attenuated the olanzapine-induced adipose deposit tissue growth. The effect was more pronounced for the combination of olanzapine with melatonin and metformin. Because most of the results were not statistically significant we can deduce that in the chronic experiment, adaptive type modifications of the receptors on which both olanzapine and melatonin act can occur.

• Adipose tissue
• melatonin
• metformin
• olanzapine pamoate
• rats

• brain PET imaging
• cognitive dysfunction
• development/fetal nutrition
• metabolism
• obesity

Heart rate recovery (HRR) is a marker of parasympathetic activity recovery after exercise, and it is associated with cardiovascular mortality and total mortality. Impaired renal function is also associated with cardiac mortality. The aim of this study was to investigate the association between HRR after exercise and renal function in patients referred for a treadmill exercise test.

This cross-sectional study was conducted at a regional hospital in southern Taiwan. Patients who completed a symptom-limited treadmill exercise test from January 2015 to February 2018 were recruited. Before the treadmill exercise test, patients were asked to complete a questionnaire on the past disease history and lifestyle factors. Serum creatinine measurement within two years prior to or after the date of the treadmill exercise test of the patients was also obtained from the medical records for these patients. Estimated glomerular filtration rate (eGFR) was calculated. Simple and multiple linear regression analyses were performed to investigate the association between one-minute HRR and eGFR.

A total of 2,825 patients completed the treadmill exercise test, and serum creatinine measurement was identified from medical records for 2,153 patients (76.2%). Multiple linear regression analysis revealed that a lower eGFR was significantly associated with lower one-minute HRR (P< 0.001), adjusting for other significant independent factors, including age, waist circumference, type 2 diabetes mellitus, and smoking.

In this cross-sectional observational study, a lower eGFR was significantly and independently associated with decreased one-minute HRR, suggesting that parasympathetic activity recovery after exercise could be impaired by a decrease in renal function.

• Adult
• Aged
• Creatinine/blood
• Cross-Sectional Studies
• Electrocardiography
• Exercise/physiology
• Exercise Test
• Female
• Glomerular Filtration Rate/physiology
• Heart Rate/physiology
• Humans
• Male
• Middle Aged
• Parasympathetic Nervous System/physiology
• Risk Factors
• Surveys and Questionnaires
• Waist Circumference/physiology

• Aging
• Autonomic nervous system
• Heart rate
• Obesity, metabolically benign
• Parasympathetic nervous system
• Sympathetic nervous system

• autonomic nervous system
• diabetes mellitus
• risk factors
• type 1
• young adult

• Adolescent
• Adult
• Blood Pressure/physiology
• Cardiovascular Diseases/complications
• Cardiovascular Diseases/physiopathology
• Case-Control Studies
• Cross-Sectional Studies
• Diabetes Mellitus, Type 1/complications
• Diabetes Mellitus, Type 1/physiopathology
• Female
• Heart Rate/physiology
• Humans
• Male
• Parasympathetic Nervous System/physiology
• Parasympathetic Nervous System/physiopathology
• Risk Factors

• 2013 / 19055-0 Fundação de Amparo à Pesquisa do Estado de São Paulo

With few effective treatments available, the global rise of metabolic diseases, including obesity, type 2 diabetes mellitus, and cardiovascular disease, seems unstoppable. Likely caused by an obesogenic environment interacting with genetic susceptibility, the pathophysiology of obesity and metabolic diseases is highly complex and involves crosstalk between many organs and systems, including the brain. The vagus nerve is in a key position to bidirectionally link several peripheral metabolic organs with the brain and is increasingly targeted for neuromodulation therapy to treat metabolic disease. Here, we review the basics of vagal functional anatomy and its implications for vagal neuromodulation therapies. We find that most existing vagal neuromodulation techniques either ignore or misinterpret the rich functional specificity of both vagal efferents and afferents as demonstrated by a large body of literature. This lack of specificity of manipulating vagal fibers is likely the reason for the relatively poor beneficial long‐term effects of such therapies. For these therapies to become more effective, rigorous validation of all physiological endpoints and optimization of stimulation parameters as well as electrode placements will be necessary. However, given the large number of function‐specific fibers in any vagal branch, genetically guided neuromodulation techniques are more likely to succeed.

• anti-inflammatory pathways
• diabetes
• electrical stimulation
• genetically guided
• gut-brain communication
• neuromodulation
• obesity
• vagotomy

Exposure to light at night (LAN) has been associated with serious pathologies, including obesity, diabetes and cancer. Recently we showed that 2 h of LAN impaired glucose tolerance in rats. Several studies have suggested that the autonomic nervous system (ANS) plays an important role in communicating these acute effects of LAN to the periphery. Here, we investigated the acute effects of LAN on the liver transcriptome of male Wistar rats. Expression levels of individual genes were not markedly affected by LAN, nevertheless pathway analysis revealed clustered changes in a number of endocrine pathways. Subsequently, we used selective hepatic denervations [sympathetic (Sx), parasympathetic (Px), total (Tx, i.e., Sx plus Px), sham] to investigate the involvement of the ANS in the effects observed. Surgical removal of the sympathetic or parasympathetic hepatic branches of the ANS resulted in many, but small changes in the liver transcriptome, including a pathway involved with circadian clock regulation, but it clearly separated the four denervation groups. On the other hand, analysis of the liver metabolome was not able to separate the denervation groups, and only 6 out of 78 metabolites were significantly up- or downregulated after denervations. Finally, removal of the sympathetic and parasympathetic hepatic nerves combined with LAN exposure clearly modulated the effects of LAN on the liver transcriptome, but left most endocrine pathways unaffected.

Conclusion: One-hour light-at-night acutely affects the liver transcriptome. Part of this effect is mediated via the nervous innervation, as a hepatectomy modulated and reduced the effect of LAN on liver transcripts.

• biological clock
• circadian
• metabolome
• neural pathway
• transcriptome

• RNA sequencing
• adipokines
• batokines
• beige adipose tissue
• brown adipose tissue
• denervation
• fatty acid oxidation
• high-fat diet
• innervation
• lipolysis
• sympathetic nervous system
• thermogenesis
• white adipose tissue

• Adipose Tissue/innervation
• Adipose Tissue/metabolism
• Adipose Tissue, Beige/metabolism
• Adipose Tissue, Brown/metabolism
• Adipose Tissue, White/metabolism
• Animals
• Biomarkers
• Energy Metabolism
• Fatty Acids/metabolism
• Homeostasis
• Humans
• Neurosecretory Systems/metabolism
• Oxidation-Reduction
• Sympathetic Nervous System
• Thermogenesis

• 16GRNT31110008 American Heart Association
• G2017031588446675 Sigma Xi

• BAT
• WAT
• adipose innervation
• adipose neuropathy
• adipose peripheral nerves
• brain–adipose communication
• neural plasticity
• sympathetic
• thermogenesis

• R01 DK114320 NIDDK NIH HHS

Weight reduction frequently occurs in patients receiving vagus nerve stimulation (VNS) therapy. Therefore, we hypothesized that during dietary intervention for weight loss, auricular electric stimulation (AES), an alternative of VNS, accelerates weight loss by increasing white adipose tissue (WAT) browning and increases energy expenditure.

C57BL/6J male mice were fed a high-fat diet for 5 wk. to induce obesity, then switched to a low-fat diet for 5 wk. and allocated into 3 groups to receive 2 Hz electric stimulation on ears, electrode clamps only, or nothing (AES, Sham and Ctrl, respectively).

Switching to a low-fat diet reduced body weight progressively in all 3 groups, with the greatest reduction in the AES group. In accordance with a mild decrease in feed intake, hypothalamus mRNA levels of Npy, AgRP tended to be reduced, while Pomc tended to be increased by AES. Mice in the AES group had the highest concentrations of norepinephrine in serum and inguinal WAT, and expression levels of uncoupling protein-1 (UCP-1) and tyrosine hydroxylase in inguinal WAT. Furthermore, their subcutaneous adipocytes had multilocular and UCP-1⁺ characteristics, along with a smaller cell size.

AES, by increasing WAT browning, could be used in conjunction with a low-fat diet to augment weight loss in addition to suppressing appetite.

• Anti-obesity
• Auricular electric stimulation
• Browning of white adipose tissue
• Dietary control
• UCP-1

• adipocyte
• dopamine receptors
• inflammation

• 3T3-L1 Cells
• Adipocytes/metabolism
• Animals
• Cells, Cultured
• Humans
• Interleukin-6/metabolism
• Leptin/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Receptors, Dopamine D2/metabolism
• Up-Regulation

• P01 HL068686 NHLBI NIH HHS
• P01 HL074940 NHLBI NIH HHS
• National Heart, Lung, and Blood Institute
• Foundation of Maryland
• National Kidney Foundation of Maryland
• Diabetes Action Research and Education Foundation

• Adipose tissue
• Diabetes mellitus
• Neuropathy
• Peripheral nerves

• Chonbuk National University Hospital

Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice (Mc4r^−/−).

Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r^−/− mice.

Results: In the first study, SDV prevented >20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study. Initially, SDV mice had reduced weekly FI; however, FI normalized to that of controls and baseline FI within the 8-week study period. In the second study, the severe obesity that is characteristic of the adult Mc4r^−/− genotype was significantly improved by SDV with a magnitude of 30% loss in excess BW over a 4-week period. Consistent with the first preventative study, within the treatment arm, SDV mice also demonstrated a transient reduction in FI relative to control and baseline levels that normalized over subsequent weeks. In addition to the accompanying loss in weight, mice subjected to SDV showed a decrease in respiratory exchange ratio (RER), and an increase in locomotor activity (LA). Analysis of the white fat-pad deposits of these mice showed that they were significantly less than the control groups.

Conclusions: Altogether, our data demonstrates that SDV both prevents gain in BW and causes weight loss in severely obese Mc4r^−/− mice. Moreover, it suggests that an important aspect of weight reduction for this type of monogenic obesity involves loss of signaling in vagal motor neurons.

• body weight
• energy expenditure
• food intake
• melanocortin
• surgery
• vagotomy
• weight loss

• Adipose Tissue/innervation
• Adipose Tissue/physiology
• Animals
• Brain/physiology
• Energy Metabolism
• Humans
• Leptin/physiology
• Lipolysis
• Neurons/physiology
• Sympathetic Nervous System/physiology
• Thermogenesis

• R01 DK053301 NIDDK NIH HHS
• R01 DK088423 NIDDK NIH HHS
• R01 DK100659 NIDDK NIH HHS
• R37 DK053301 NIDDK NIH HHS

• circadian
• circwave
• lipid metabolism
• retroperitoneal WAT
• visceral WAT

• adipose tissue
• autonomic nervous system
• energy expenditure
• gut hormones
• obesity
• vagal nerve blockade
• vagal nerve stimulation
• weight loss

• acipimox
• heart rate variability
• lipolysis

The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development.

• adipose tissue
• autonomic nervous system
• body composition
• orexin
• thermogenesis

• melatonin
• metabolic syndrome
• second-generation antipsychotics

• epicardial fat thickness
• waist circumference
• body mass index
• autonomic nervous system

• Adolescent
• Adult
• Age Factors
• Aged
• Autonomic Nervous System Diseases/epidemiology
• Autonomic Nervous System Diseases/physiopathology
• Blood Pressure
• Body Mass Index
• Body Weights and Measures
• Electrocardiography
• Electromyography
• Exercise Test
• Female
• Heart Rate/physiology
• Humans
• Lipids/blood
• Male
• Middle Aged
• Obesity/epidemiology
• Obesity/physiopathology
• Risk Factors
• Waist Circumference
• Young Adult

• Adipocytokines
• Adipose tissue
• Insulin resistance
• Parasympathetic activity
• Sympathetic activity
• Visceral obesity syndrome

Catecholamines are known to increase renal glucose release during hypoglycemia. The specific extent of the contribution of different sources of catecholamines, endocrine delivery via circulation or release from autonomous sympathetic renal nerves, though, is unknown. We tested the hypothesis that sympathetic renal innervation plays a major role in the regulation of renal gluconeogenesis. For this purpose, instrumented adolescent pigs had one kidney surgically denervated while the other kidney served as a control. A hypoglycemic clamp with arterial blood glucose below 2 mmol/L was maintained for 75 min. Arteriovenous blood glucose difference, inulin clearance, p-aminohippurate clearance, and sodium excretion were measured in intervals of 15 min separately for both kidneys. Blood glucose was lowered to 0.84 ± 0.33 mmol/L for 75 min. The side-dependent renal net glucose release (SGN) decreased significantly after the unilateral ablation of renal nerves. In the linear mixed model, renal denervation had a significant inhibitory effect on renal net glucose release (P = 0.036). The SGN of the ablated kidney decreased by 0.02 mmol/min and was equivalent to 43.3 ± 23.2% of the control (nonablated) kidney in the pigs. This allows the conclusion that renal glucose release is partly controlled by sympathetic nerves. This may be relevant in humans as well, and could explain the increased risk of severe hypoglycemia of patients with diabetes mellitus and autonomous neuropathy. The effects of denervation on renal glucose metabolism should be critically taken into account when considering renal denervation as a therapy in diabetic patients.

• Glucose release
• hypoglycemia
• renal denervation
• side dependent

• 3T3-L1 Cells
• Animals
• Autophagy
• Chromatography, High Pressure Liquid
• Genetic Vectors/genetics
• Genetic Vectors/metabolism
• Lamin Type A/analysis
• Lamin Type A/genetics
• Lamin Type A/metabolism
• Lentivirus/genetics
• Mice
• Mitochondria/metabolism
• Proteolysis
• Proteomics
• Reactive Oxygen Species/metabolism
• Real-Time Polymerase Chain Reaction
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude of the SCN’s electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise) has a positive effect on amplitude. Given that the amplitude of the SCN’s electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-h rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders.

• SCN
• aging
• disease
• diurnal
• electrophysiology
• exercise
• photoperiod
• plasticity

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

• brain tumors
• craniopharyngioma
• hypothalamic obesity
• irradiation
• neurocognitive
• neuroendocrinology
• neurosurgery
• pituitary
• quality of life
• recurrence
• sleep

• Denervation
• Herpes simplex virus-1
• Humans
• Insulin
• Leptin
• Mice
• Norepinephrine turnover
• Pseudorabies virus
• Rats
• Siberian hamsters

• Adipose Tissue, White/metabolism
• Animals
• Humans
• Insulin/metabolism
• Lipid Metabolism/physiology
• Lipolysis/physiology
• Norepinephrine/metabolism
• Sympathetic Nervous System/metabolism

• R37 DK035254 NIDDK NIH HHS
• R37 DK 35254 NIDDK NIH HHS

• dorsal root ganglia
• electrophysiology
• tract tracing
• white adipose tissue

• Action Potentials/drug effects
• Action Potentials/physiology
• Adipose Tissue, White/innervation
• Adipose Tissue, White/physiology
• Animals
• Arcuate Nucleus of Hypothalamus/drug effects
• Arcuate Nucleus of Hypothalamus/physiology
• Cricetinae
• Dose-Response Relationship, Drug
• Ganglia, Spinal/drug effects
• Ganglia, Spinal/physiology
• Leptin/pharmacology
• Leptin/physiology
• Male
• Peripheral Nerves/drug effects
• Peripheral Nerves/physiology
• Phodopus
• Sensory Receptor Cells/drug effects
• Sensory Receptor Cells/physiology
• Spinal Cord/drug effects
• Spinal Cord/physiology

• DK-R01026687 NIDDK NIH HHS
• DK-R3735254 NIDDK NIH HHS
• P30 DK026687 NIDDK NIH HHS
• R37 DK035254 NIDDK NIH HHS
• DK-R01020541 NIDDK NIH HHS

• adipose
• fatty acids
• insulin resistance
• lipogenesis
• lipolysis
• obesity
• review
• triacylglycerol

• Adipose Tissue/immunology
• Adipose Tissue/metabolism
• Animals
• Cytokines/metabolism
• Diabetes Mellitus, Type 2/immunology
• Diabetes Mellitus, Type 2/metabolism
• Energy Metabolism
• Humans
• Insulin/metabolism
• Insulin Resistance
• Lipogenesis
• Lipolysis
• Liver/immunology
• Liver/metabolism
• Obesity/immunology
• Obesity/metabolism
• Signal Transduction
• Triglycerides/biosynthesis
• Triglycerides/metabolism

• DK085753 NIDDK NIH HHS
• R01 DK085753 NIDDK NIH HHS
• DK030898 NIDDK NIH HHS
• R37 DK030898 NIDDK NIH HHS
• R01 DK030898 NIDDK NIH HHS

In the liver, clock genes are proposed to drive metabolic rhythms. These gene rhythms are driven by the suprachiasmatic nucleus (SCN) mainly by food intake and via autonomic and hormonal pathways. Forced activity during the normal rest phase, induces also food intake, thus neglecting the signals of the SCN, leading to conflicting time signals to target tissues of the SCN. The present study explored in a rodent model of night-work the influence of food during the normal sleep period on the synchrony of gene expression between clock genes and metabolic genes in the liver. Male Wistar rats were exposed to forced activity for 8 h either during the rest phase (day) or during the active phase (night) by using a slow rotating wheel. In this shift work model food intake shifts spontaneously to the forced activity period, therefore the influence of food alone without induced activity was tested in other groups of animals that were fed ad libitum, or fed during their rest or active phase. Rats forced to be active and/or eating during their rest phase, inverted their daily peak of Per1, Bmal1 and Clock and lost the rhythm of Per2 in the liver, moreover NAMPT and metabolic genes such as Pparα lost their rhythm and thus their synchrony with clock genes. We conclude that shift work or food intake in the rest phase leads to desynchronization within the liver, characterized by misaligned temporal patterns of clock genes and metabolic genes. This may be the cause of the development of the metabolic syndrome and obesity in individuals engaged in shift work.