scholarly journals Off the Clock: From Circadian Disruption to Metabolic Disease

2019 ◽  
Vol 20 (7) ◽  
pp. 1597 ◽  
Author(s):  
Eleonore Maury
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Jet Lag ◽  
High Fat ◽  
Peripheral Tissues ◽  
Temporal Regulation ◽  
The Impact ◽  
Fat Feeding ◽  
The Brain ◽  
Daily Changes

Circadian timekeeping allows appropriate temporal regulation of an organism’s internal metabolism to anticipate and respond to recurrent daily changes in the environment. Evidence from animal genetic models and from humans under circadian misalignment (such as shift work or jet lag) shows that disruption of circadian rhythms contributes to the development of obesity and metabolic disease. Inappropriate timing of food intake and high-fat feeding also lead to disruptions of the temporal coordination of metabolism and physiology and subsequently promote its pathogenesis. This review illustrates the impact of genetically or environmentally induced molecular clock disruption (at the level of the brain and peripheral tissues) and the interplay between the circadian system and metabolic processes. Here, we discuss some mechanisms responsible for diet-induced circadian desynchrony and consider the impact of nutritional cues in inter-organ communication, with a particular focus on the communication between peripheral organs and brain. Finally, we discuss the relay of environmental information by signal-dependent transcription factors to adjust the timing of gene oscillations. Collectively, a better knowledge of the mechanisms by which the circadian clock function can be compromised will lead to novel preventive and therapeutic strategies for obesity and other metabolic disorders arising from circadian desynchrony.

scholarly journals Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 940
Author(s):  
Li Wu ◽  
Yuqiu Han ◽  
Zhipeng Zheng ◽  
Shuai Zhu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Intestinal Barrier ◽  
Behavioral Performance ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Obeticholic Acid ◽  
Promising Agent ◽  
Serum Biochemical ◽  
Lipid Metabolites ◽  
The Brain

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

The impact of maternal high-fat feeding on liver and abdominal fat accumulation in adult offspring under a long-term high-fat diet

Hepatology ◽  
2009 ◽  
Vol 51 (6) ◽  
pp. 2234-2235 ◽  
Author(s):  
Adriana L. Burgueño ◽  
Julieta Carabelli ◽  
Silvia Sookoian ◽  
Carlos J. Pirola
Keyword(s):  
High Fat Diet ◽  
Abdominal Fat ◽  
Adult Offspring ◽  
High Fat ◽  
Fat Accumulation ◽  
The Impact ◽  
Fat Feeding

scholarly journals Differential Effects of Maternal High Fat Diet During Pregnancy and Lactation on Taste Preferences in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3553
Author(s):  
Gabor C. Mezei ◽  
Serdar H. Ural ◽  
Andras Hajnal
Keyword(s):  
High Fat Diet ◽  
Metabolic Disorders ◽  
Taste Preference ◽  
Normal Diet ◽  
Taste Preferences ◽  
Adult Offspring ◽  
High Fat ◽  
Preference Testing ◽  
Pregnancy And Lactation ◽  
The Impact

Maternal intake of high fat diet (HFD) increases risk for obesity and metabolic disorders in offspring. Developmental programming of taste preference is a potential mechanism by which this occurs. Whether maternal HFD during pregnancy, lactation, or both, imposes greater risks for altered taste preferences in adult offspring remains a question, and in turn, was investigated in the present study. Four groups of offspring were generated based on maternal HFD access: (1) HFD during pregnancy and lactation (HFD); (2) HFD during pregnancy (HFD-pregnancy); (3) HFD during lactation (HFD-lactation); and (4) normal diet (ND) during pregnancy and lactation (ND). Adult offspring 70 days of age underwent sensory and motivational taste preference testing with various concentrations of sucrose and Intralipid solutions using brief-access automated gustometers (Davis-rigs) and 24 h two-bottle choice tests, respectively. To control for post-gestational diet effects, offspring in all experimental groups were weaned on ND, and did not differ in body weight or glucose tolerance at the time of testing. Offspring exposed to maternal HFD showed increased sensory taste responses for 0.3, 0.6, 1.2 M sucrose solutions in HFD and 0.6 M in HFD-pregnancy groups, compared to animals exposed to ND. Similar effects were noted for lower concentrations of Intralipid in HFD (0.05, 0.10%) and HFD-pregnancy (0.05, 0.10, 0.5%) groups. The HFD-lactation group showed an opposite, diminished responsiveness for sucrose at the highest concentrations (0.9, 1.2, 1.5 M), but not for Intralipid, compared to ND animals. Extended-access two-bottle tests did not reveal major difference across the groups. Our study shows that maternal HFD during pregnancy and lactation has markedly different effects on preferences for palatable sweet and fatty solutions in adult offspring and suggests that such developmental programing may primarily affect gustatory mechanisms. Future studies are warranted for determining the impact of taste changes on development of obesity and metabolic disorders in a “real” food environment with food choices available, as well as to identify specific underlying mechanisms.

scholarly journals Effects of resveratrol on changes induced by high-fat feeding on clock genes in rats

2013 ◽  
Vol 110 (8) ◽  
pp. 1421-1428 ◽  
Author(s):  
Jonatan Miranda ◽  
María P. Portillo ◽  
Juan Antonio Madrid ◽  
Noemí Arias ◽  
M. Terasa Macarulla ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Fatty Acid Synthase ◽  
Clock Genes ◽  
The Body ◽  
Control Group ◽  
Standard Diet ◽  
High Fat ◽  
Peripheral Tissues ◽  
Fat Feeding

In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding in the expression of clock genes and clock-controlled genes in the white adipose tissue from rats. For this purpose, rats were divided into three groups: a control group, fed a standard diet, and two other groups, either fed a high-fat diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression of clock genes and clock-controlled genes was analysed by RT-PCR. Protein expression and fatty acid synthase (FAS) activity were also analysed. When comparing the controls, the RSV group showed similar patterns of response to the HF group, except for reverse erythroblastosis virus α (Rev-Erbα), which was down-regulated. The expression of this gene reached the same levels as in control rats. The response pattern of protein expression forRev-Erbαwas similar to that found for gene expression. High-fat feeding up-regulated all adipogenic genes and resveratrol did not modify them. In the HF group, the activity of FAS tended to increase, while resveratrol decreased. In conclusion, resveratrol reverses the change induced by high-fat feeding in the expression ofRev-Erbαin adipose tissue, which means that clock machinery is a target for this polyphenol. This change seems to be related to reduced lipogenesis, which might be involved in the body fat-lowering effect of this molecule.

scholarly journals Genetic-epigenetic interactions in paternal transgenerational inheritance of metabolic disorders

2021 ◽  
Author(s):  
Anne-Sophie Pepin ◽  
Christine Lafleur ◽  
Romain Lambrot ◽  
Vanessa Dumeaux ◽  
Sarah Kimmins
Keyword(s):  
Metabolic Disease ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Genetic Model ◽  
Epigenetic Inheritance ◽  
Sperm Chromatin ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Adult Disease

Parental environmental exposures can strongly influence descendant risks for adult disease. Metabolic disorders arise from the intersection of environmental and genetic risk factors, with epigenetic inheritance being at the center of the familial cycle of transgenerational disease. How paternal high-fat diet changes the sperm chromatin leading to the acquisition of metabolic disease in offspring remains controversial and ill-defined. Using a genetic model of epigenetic inheritance, we investigated the role of histone H3 lysine 4 methylation (H3K4me3) in the paternal transmission of metabolic dysfunction. We show that obesity-induced alterations in sperm H3K4me3 associated with offspring phenotypes and corresponded to embryonic and placental chromatin profiles and gene expression. Transgenerational susceptibility to metabolic disease was only observed when grandsires had a pre-existing genetic predisposition to metabolic dysfunction that was associated with enhanced alterations to sperm H3K4me3. This non-DNA based knowledge of inheritance has the potential to improve our understanding of how environment shapes heritability and may lead to novel routes for the prevention of disease.

scholarly journals Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins

PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009802
Author(s):  
Sumeet A. Khetarpal ◽  
Cecilia Vitali ◽  
Michael G. Levin ◽  
Derek Klarin ◽  
Joseph Park ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endothelial Lipase ◽  
Primary Role ◽  
Loss Of Function ◽  
Extracellular Lipase ◽  
High Fat ◽  
Peripheral Tissues ◽  
The Impact

Triglyceride-rich lipoproteins (TRLs) are circulating reservoirs of fatty acids used as vital energy sources for peripheral tissues. Lipoprotein lipase (LPL) is a predominant enzyme mediating triglyceride (TG) lipolysis and TRL clearance to provide fatty acids to tissues in animals. Physiological and human genetic evidence support a primary role for LPL in hydrolyzing TRL TGs. We hypothesized that endothelial lipase (EL), another extracellular lipase that primarily hydrolyzes lipoprotein phospholipids may also contribute to TRL metabolism. To explore this, we studied the impact of genetic EL loss-of-function on TRL metabolism in humans and mice. Humans carrying a loss-of-function missense variant in LIPG, p.Asn396Ser (rs77960347), demonstrated elevated plasma TGs and elevated phospholipids in TRLs, among other lipoprotein classes. Mice with germline EL deficiency challenged with excess dietary TG through refeeding or a high-fat diet exhibited elevated TGs, delayed dietary TRL clearance, and impaired TRL TG lipolysis in vivo that was rescued by EL reconstitution in the liver. Lipidomic analyses of postprandial plasma from high-fat fed Lipg-/- mice demonstrated accumulation of phospholipids and TGs harboring long-chain polyunsaturated fatty acids (PUFAs), known substrates for EL lipolysis. In vitro and in vivo, EL and LPL together promoted greater TG lipolysis than either extracellular lipase alone. Our data positions EL as a key collaborator of LPL to mediate efficient lipolysis of TRLs in humans and mice.

scholarly journals Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding

2009 ◽  
Vol 15 (4) ◽  
pp. 442-446 ◽  
Author(s):  
Chi-Liang Eric Yen ◽  
Mei-Leng Cheong ◽  
Carrie Grueter ◽  
Ping Zhou ◽  
Junya Moriwaki ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
High Fat ◽  
Intestinal Enzyme ◽  
Fat Feeding

scholarly journals A low dose of beryllium exposure influences gut microbiota and promotes metabolic syndrome.

2020 ◽  
Author(s):  
Kwang Hyun Cha ◽  
Jung-Seok Yang ◽  
Dae-Geun Song ◽  
Kye-Yoon Yoon ◽  
Erdenedolgor Erdene-Ochir ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Gut Microbiota ◽  
Metabolic Disorder ◽  
Metabolic Disorders ◽  
Causal Effect ◽  
Body Weight Gain ◽  
Significant Implication ◽  
Toxic Heavy Metals ◽  
The Impact

Abstract Background Elements, including essential minerals and metals, play an important role in human biological functions. Some studies have suggested that exposure to certain elements such as arsenic and cadmium can disturb gut microbiota and result in metabolic disorders. Despite considerable evidence that exposure to toxic heavy metals is significantly associated with host metabolic disorder, few studies have investigated the relationships between fecal elements, gut microbiota, and host metabolism. In order to gain a deeper understanding of the impact of various fecal elements on gut microbiota and metabolic disorder, we have to investigate fecal elements from human stools for association study and demonstrate that certain elements have the causal effect on metabolic disease and changes in gut microbiota. Results We analyzed 28 elements from 304 feces of human twins and evaluated the effects of fecal elements on both gut microbiota and metabolic disorder. Fecal beryllium content was found significantly correlated with biomarkers of metabolic disease and metabolic disease-related gut microbiota such as Akkermansia and Bifidobacterium . In vitro human fecal culture showed marked reduction of species evenness and Bifidobacterium abundance after beryllium treatment. Notably, in mice fed a high-fat diet, 30 ppb of beryllium exposure resulted in significant body weight gain and increased plasma biomarkers for metabolic disorder with an altered microbial community. Beryllium exposure also affected cecal short chain fatty acid profiles, colonic function, and inflammation. Conclusions Our findings indicate that low doses of beryllium, almost similar to the current criteria for beryllium in drinking water, perturb the gut microbiota and worsen metabolic disorders, which is significant implication in public health.

scholarly journals High-fat diet-induced diabetes leads to vascular alterations, pericyte reduction, and perivascular depletion of microglia in a 6-OHDA toxin model of Parkinson disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Osama F. Elabi ◽  
João Paulo M. C. M. Cunha ◽  
Abderahim Gaceb ◽  
Malin Fex ◽  
Gesine Paul
Keyword(s):  
High Fat Diet ◽  
Cell Loss ◽  
Vascular Pathology ◽  
Motor Deficits ◽  
High Fat ◽  
Branching Points ◽  
Brain Microvasculature ◽  
The Impact ◽  
The Brain

Abstract Background Diabetes has been recognized as a risk factor contributing to the incidence and progression of Parkinson’s disease (PD). Although several hypotheses suggest a number of different mechanisms underlying the aggravation of PD caused by diabetes, less attention has been paid to the fact that diabetes and PD share pathological microvascular alterations in the brain. The characteristics of the interaction of diabetes in combination with PD at the vascular interface are currently not known. Methods We combined a high-fat diet (HFD) model of diabetes mellitus type 2 (DMT2) with the 6-OHDA lesion model of PD in male mice. We analyzed the association between insulin resistance and the achieved degree of dopaminergic nigrostriatal pathology. We further assessed the impact of the interaction of the two pathologies on motor deficits using a battery of behavioral tests and on microglial activation using immunohistochemistry. Vascular pathology was investigated histologically by analyzing vessel density and branching points, pericyte density, blood–brain barrier leakage, and the interaction between microvessels and microglia in the striatum. Results Different degrees of PD lesion were obtained resulting in moderate and severe dopaminergic cell loss. Even though the HFD paradigm did not affect the degree of nigrostriatal lesion in the acute toxin-induced PD model used, we observed a partial aggravation of the motor performance of parkinsonian mice by the diet. Importantly, the combination of a moderate PD pathology and HFD resulted in a significant pericyte depletion, an absence of an angiogenic response, and a significant reduction in microglia/vascular interaction pointing to an aggravation of vascular pathology. Conclusion This study provides the first evidence for an interaction of DMT2 and PD at the brain microvasculature involving changes in the interaction of microglia with microvessels. These pathological changes may contribute to the pathological mechanisms underlying the accelerated progression of PD when associated with diabetes.

scholarly journals Parental SIRT1 Overexpression Attenuate Metabolic Disorders Due to Maternal High-Fat Feeding

2020 ◽  
Vol 21 (19) ◽  
pp. 7342
Author(s):  
Long T. Nguyen ◽  
Sonia Saad ◽  
Hui Chen ◽  
Carol A. Pollock
Keyword(s):  
Body Weight ◽  
Stress Responses ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
High Fat ◽  
Metabolic Markers ◽  
Lower Body Weight ◽  
Hepatic Glucose ◽  
Fat Feeding

Maternal obesity can contribute to the development of obesity and related metabolic disorders in progeny. Sirtuin (SIRT)1, an essential regulator of metabolism and stress responses, has recently emerged as an important modifying factor of developmental programming. In this study, to elucidate the effects of parental SIRT1 overexpression on offspring mechanism, four experimental groups were included: (1) Chow-fed wild-type (WT)-dam × Chow-fed WT-sire; (2) High-fat diet (HFD)-fed WT-dam × Chow-fed WT-sire; (3) HFD-fed hemizygous SIRT1-transgenic (Tg)-dam × Chow-fed WT-sire; and (4) HFD-fed WT dam × Chow-fed Tg-sire. Our results indicate that Tg breeders had lower body weight and fat mass compared to WT counterparts and gave birth to WT offspring with reductions in body weight, adiposity and hyperlipidaemia compared to those born of WT parents. Maternal SIRT1 overexpression also reversed glucose intolerance, and normalised abnormal fat morphology and the expression of dysregulated lipid metabolism markers, including SIRT1. Despite having persistent hepatic steatosis, offspring born to Tg parents showed an improved balance of hepatic glucose/lipid metabolic markers, as well as reduced levels of inflammatory markers and TGF-β/Smad3 fibrotic signalling. Collectively, the data suggest that parental SIRT1 overexpression can ameliorate adverse metabolic programming effects by maternal obesity.

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