scholarly journals Protein Malnutrition during Pregnancy in C57BL/6J Mice Results in Offspring with Altered Circadian Physiology before Obesity

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1570-1580 ◽  
Author(s):  
Gregory M. Sutton ◽  
Armand V. Centanni ◽  
Andrew A. Butler
Keyword(s):  
Feeding Behavior ◽  
Energy Homeostasis ◽  
Control Diet ◽  
Whole Body ◽  
Deficient Diet ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Fetal Malnutrition ◽  
Circadian Physiology

The mechanisms linking intrauterine growth retardation (IUGR) with adulthood obesity and diabetes are unclear. These studies investigated energy homeostasis in 8- and 20-wk-old male and female mice subjected to protein deficiency in utero. Pregnant C57BL/6J female mice were fed a protein-deficient diet (6% protein). Undernourished offspring (UO) and controls (CO) were cross-fostered to lactating dams fed a 20% control diet. The 24-h profiles of energy expenditure, feeding behavior, physical activity, and whole-body substrate preference was assessed using 8-wk UO and CO weaned onto control diet. Blood chemistries, glucose tolerance, and expression of genes involved in hepatic lipid and glucose metabolism were analyzed in 8- and 20-wk-old CO and UO fed control or a high-fat diet. UO exhibited IUGR with catch-up growth at 8 wk of age and increased severity of diet-induced obesity and insulin resistance by 20 wk of age. Therefore, fetal malnutrition in the C57BL/6J mouse increases sensitivity to diet-induced obesity. Abnormal daily rhythms in food intake and metabolism, increased lipogenesis, and inflammation preceded obesity in the UO group. Arrhythmic expression of circadian oscillator genes was evident in brain, liver, and muscle of UO at 8 and 20 wk of age. Expression of the clock-associated nuclear receptor and transcription repressor Rev-erbα was reduced in liver and muscle of UO. Altered circadian physiology may be symptomatic of the metabolic dysregulation associated with IUGR, and altered feeding behavior and substrate metabolism may contribute to the obese phenotype.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

scholarly journals Female mice exposed to low doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes

2020 ◽  
Vol 42 ◽  
pp. 101104 ◽  
Author(s):  
Myriam P. Hoyeck ◽  
Rayanna C. Merhi ◽  
Hannah L. Blair ◽  
C. Duncan Spencer ◽  
Mikayla A. Payant ◽  
...  
Keyword(s):  
Low Doses ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Pregnancy And Lactation ◽  
Increased Susceptibility

Zinc deficiency impairs whole body accumulation of polyunsaturates and increases the utilization of [1-14C]linoleate for de novo lipid synthesis in pregnant rats

1995 ◽  
Vol 73 (9) ◽  
pp. 1246-1252 ◽  
Author(s):  
S. C. Cunnane ◽  
J. Yang
Keyword(s):  
Food Intake ◽  
Zinc Deficiency ◽  
De Novo ◽  
Control Diet ◽  
Lipid Synthesis ◽  
Whole Body ◽  
Deficient Diet ◽  
Pregnant Rats ◽  
Whole Body Metabolism ◽  
Zinc Deficient Diet

Zinc deficiency impairs the metabolism of polyunsaturates, but the degree to which its effects are independent of food intake are still in question. Identical amounts of a semiliquid control diet (26.4 mg zinc/kg) or moderately zinc deficient diet (3.2 mg zinc/kg) were tube fed to rats for 11 days during the second half of pregnancy to evaluate the specific effects of zinc deficiency on maternal utilization and fetal accumulation of polyunsaturates. The whole body fatty acid balance method was used to determine net accumulation of polyunsaturates and their whole-body disappearance. Incorporation of 14C from [1-14C]linoleate into maternal and fetal lipid classes was also studied on days 20–21. At term, zinc-deficient rats had significantly higher whole-body disappearance of linoleate and α-linolenate and lower accumulation of n−6 and n−3 long-chain polyunsaturates. Zinc-deficient rats had higher 14C activity in free cholesterol, saturates, and monounsaturates in several maternal organs but not in the fetuses. We conclude that during pregnancy, moderate zinc deficiency not affecting food intake or weight gain still alters whole-body metabolism of linoleate and α-linolenate towards increased β-oxidation and also increases the utilization of carbon from linoleate for de novo lipid synthesis.Key words: cholesterol, linoleate, α-linolenate, oxidation, polyunsaturates, pregnancy, zinc.

scholarly journals CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

2016 ◽  
Vol 310 (5) ◽  
pp. E332-E345 ◽  
Author(s):  
Risa M. Wolf ◽  
Xia Lei ◽  
Zhi-Chun Yang ◽  
Maeva Nyandjo ◽  
Stefanie Y. Tan ◽  
...  
Keyword(s):  
Serum Levels ◽  
Whole Body ◽  
Activity Levels ◽  
Loss Of Function ◽  
Physiological Control ◽  
Liver Size ◽  
Male And Female ◽  
Female Mice ◽  
Obesity And Diabetes ◽  
Similar Weight

C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity.

Intestinal gluconeogenesis and protein diet: future directions

2020 ◽  
pp. 1-8
Author(s):  
Amandine Gautier-Stein ◽  
Fabienne Rajas ◽  
Gilles Mithieux
Keyword(s):  
Portal Vein ◽  
Energy Homeostasis ◽  
Glucose Sensing ◽  
Endogenous Glucose Production ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Beneficial Effects ◽  
Obesity And Diabetes ◽  
Intestinal Gluconeogenesis ◽  
Protein Diets

High-protein meals and foods are promoted for their beneficial effects on satiety, weight loss and glucose homeostasis. However, the mechanisms involved and the long-term benefits of such diets are still debated. We here review how the characterisation of intestinal gluconeogenesis (IGN) sheds new light on the mechanisms by which protein diets exert their beneficial effects on health. The small intestine is the third organ (in addition to the liver and kidney) contributing to endogenous glucose production via gluconeogenesis. The particularity of glucose produced by the intestine is that it is detected in the portal vein and initiates a nervous signal to the hypothalamic nuclei regulating energy homeostasis. In this context, we demonstrated that protein diets initiate their satiety effects indirectly via IGN and portal glucose sensing. This induction results in the activation of brain areas involved in the regulation of food intake. The μ-opioid-antagonistic properties of protein digests, exerted in the portal vein, are a key link between IGN induction and protein-enriched diet in the control of satiety. From our results, IGN can be proposed as a mandatory link between nutrient sensing and the regulation of whole-body homeostasis. The use of specific mouse models targeting IGN should allow us to identify several metabolic functions that could be controlled by protein diets. This will lead to the characterisation of the mechanisms by which protein diets improve whole-body homeostasis. These data could be the basis of novel nutritional strategies targeting the serious metabolic consequences of both obesity and diabetes.

scholarly journals Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased Akkermansia muciniphila in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2932
Author(s):  
Marion Régnier ◽  
Marialetizia Rastelli ◽  
Arianne Morissette ◽  
Francesco Suriano ◽  
Tiphaine Le Roy ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Strongly Correlated ◽  
Akkermansia Muciniphila ◽  
Diet Induced Obesity ◽  
Triglyceride Accumulation ◽  
Obesity And Diabetes ◽  
Nutritional Compounds ◽  
Improve Health

Obesity and obesity-related disorders, such as type 2 diabetes have been progressively increasing worldwide and treatments have failed to counteract their progression. Growing evidence have demonstrated that gut microbiota is associated with the incidence of these pathologies. Hence, the identification of new nutritional compounds, able to improve health through a modulation of gut microbiota, is gaining interest. In this context, the aim of this study was to investigate the gut-driving effects of rhubarb extract in a context of diet-induced obesity and diabetes. Eight weeks old C57BL6/J male mice were fed a control diet (CTRL), a high fat and high sucrose diet (HFHS) or a HFHS diet supplemented with 0.3% (g/g) of rhubarb extract for eight weeks. Rhubarb supplementation fully prevented HFHS-induced obesity, diabetes, visceral adiposity, adipose tissue inflammation and liver triglyceride accumulation, without any modification in food intake. By combining sequencing and qPCR methods, we found that all these effects were associated with a blooming of Akkermansia muciniphila, which is strongly correlated with increased expression of Reg3γ in the colon. Our data showed that rhubarb supplementation is sufficient to protect against metabolic disorders induced by a diet rich in lipid and carbohydrates in association with a reciprocal interaction between Akkermansia muciniphila and Reg3γ.

scholarly journals The Impact of Single-Cell Genomics on Adipose Tissue Research

2020 ◽  
Vol 21 (13) ◽  
pp. 4773
Author(s):  
Alana Deutsch ◽  
Daorong Feng ◽  
Jeffrey E. Pessin ◽  
Kosaku Shinoda
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Diabetes Research ◽  
Obesity And Diabetes ◽  
Important Regulator ◽  
Whole Body Metabolism ◽  
Tissue Aging ◽  
The Impact

Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation.

scholarly journals Hepsin enhances liver metabolism and inhibits adipocyte browning in mice

2020 ◽  
Vol 117 (22) ◽  
pp. 12359-12367 ◽  
Author(s):  
Shuo Li ◽  
Jianhao Peng ◽  
Hao Wang ◽  
Wei Zhang ◽  
J. Mark Brown ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Liver Glycogen ◽  
Liver Metabolism ◽  
Glucose And Lipid Metabolism ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Transmembrane Serine Protease ◽  
Marked Resistance ◽  
Hepatocyte Growth ◽  
Deficient Mice

Hepsin is a transmembrane serine protease primarily expressed in the liver. To date, the physiological function of hepsin remains poorly defined. Here we report that hepsin-deficient mice have low levels of blood glucose and lipids and liver glycogen, but increased adipose tissue browning and basal metabolic rates. The phenotype is caused by reduced hepatocyte growth factor activation and impaired Met signaling, resulting in decreased liver glucose and lipid metabolism and enhanced adipocyte browning. Hepsin-deficient mice exhibit marked resistance to high-fat diet-induced obesity, hyperglycemia, and hyperlipidemia. Indb/dbmice, hepsin deficiency ameliorates obesity and diabetes. These data indicate that hepsin is a key regulator in liver metabolism and energy homeostasis, suggesting that hepsin could be a therapeutic target for treating obesity and diabetes.

scholarly journals Dnmt3b Deficiency in Myf5+-Brown Fat Precursor Cells Promotes Obesity in Female Mice

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1087
Author(s):  
Shirong Wang ◽  
Qiang Cao ◽  
Xin Cui ◽  
Jia Jing ◽  
Fenfen Li ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Dna Methyltransferase ◽  
Energy Homeostasis ◽  
De Novo ◽  
Genetic Model ◽  
Precursor Cells ◽  
Brown Fat ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Treatment Of Obesity

Increasing energy expenditure through activation of brown fat thermogenesis is a promising therapeutic strategy for the treatment of obesity. Epigenetic regulation has emerged as a key player in regulating brown fat development and thermogenic program. Here, we aimed to study the role of DNA methyltransferase 3b (Dnmt3b), a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat function and energy homeostasis. We generated a genetic model with Dnmt3b deletion in brown fat-skeletal lineage precursor cells (3bKO mice) by crossing Dnmt3b-floxed (fl/fl) mice with Myf5-Cre mice. Female 3bKO mice are prone to diet-induced obesity, which is associated with decreased energy expenditure. Dnmt3b deficiency also impairs cold-induced thermogenic program in brown fat. Surprisingly, further RNA-seq analysis reveals a profound up-regulation of myogenic markers in brown fat of 3bKO mice, suggesting a myocyte-like remodeling in brown fat. Further motif enrichment and pyrosequencing analysis suggests myocyte enhancer factor 2C (Mef2c) as a mediator for the myogenic alteration in Dnmt3b-deficient brown fat, as indicated by decreased methylation at its promoter. Our data demonstrate that brown fat Dnmt3b is a key regulator of brown fat development, energy metabolism and obesity in female mice.

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