scholarly journals Gsα Deficiency in the Ventromedial Hypothalamus Enhances Leptin Sensitivity and Improves Glucose Homeostasis in Mice on a High-Fat Diet

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 600-610 ◽  
Author(s):  
Alta Berger ◽  
Ahmed Kablan ◽  
Catherine Yao ◽  
Thuy Ho ◽  
Brandon Podyma ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Ventromedial Hypothalamus ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Paternal Allele ◽  
Molecular Evidence ◽  
High Fat ◽  
Leptin Sensitivity ◽  
Parent Of Origin

Abstract In both mice and patients with Albright hereditary osteodystrophy, heterozygous inactivating mutations of Gsα, a ubiquitously expressed G protein that mediates receptor-stimulated intracellular cAMP production, lead to obesity and insulin resistance but only when the mutation is present on the maternal allele. This parent-of-origin effect in mice was shown to be due to Gsα imprinting in one or more brain regions. The ventromedial hypothalamus (VMH) is involved in the regulation of energy and glucose homeostasis, but the role of Gsα in VMH on metabolic regulation is unknown. To examine this, we created VMH-specific Gsα-deficient mice by mating Gsα-floxed mice with SF1-cre mice. Heterozygotes with Gsα mutation on either the maternal or paternal allele had a normal metabolic phenotype, and there was no molecular evidence of Gsα imprinting, indicating that the parent-of-origin metabolic effects associated with Gsα mutations is not due to Gsα deficiency in VMH SF1 neurons. Homozygous VMH Gsα knockout mice (VMHGsKO) showed no changes in body weight on either a regular or high-fat diet. However, glucose metabolism (fasting glucose, glucose tolerance, insulin sensitivity) was significantly improved in male VMHGsKO mice, with the difference more dramatic on the high-fat diet. In addition, male VMHGsKO mice on the high-fat diet showed a greater anorexigenic effect and increased VMH signal transducer and activator of transcription-3 phosphorylation in response to leptin. These results indicate that VMH Gsα/cyclic AMP signaling regulates glucose homeostasis and alters leptin sensitivity in mice, particularly in the setting of excess caloric intake.

Chronic social stress lessens the metabolic effects induced by a high fat diet

2021 ◽  
Author(s):  
Tanja Jene ◽  
Inigo Ruiz de Azua ◽  
Annika Hasch ◽  
Jennifer Klüpfel ◽  
Julia Deuster ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Negative Consequences ◽  
High Fat ◽  
Glucose Levels ◽  
Metabolic Dysregulation

Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high fat diet (HFD), aggravates the metabolic phenotype, and whether there are particularly sensitive time windows for the negative consequences of HFD exposure. Chronically stressed male mice and controls (CTRL) were kept under (i) SD-conditions, (ii) with HFD commencing post-CSD, or (iii) provided with HFD lasting throughout, and after CSD. Under SD conditions, stress increased glucose levels early post-CSD. Both HFD regimens increased glucose levels in non-stressed mice, but not in stressed mice. Nonetheless, when HFD was provided after CSD, stressed mice did not differ from controls in long-term body weight gain, fat tissue mass and plasma insulin, and leptin levels. In contrast, when HFD was continuously available, stressed mice displayed reduced body weight gain, lowered plasma levels of insulin, and leptin, and reduced white adipose tissue weights as compared to their HFD-treated non-stressed controls. Interestingly, stress-induced adrenal hyperplasia and hypercortisolemia were observed in mice treated with SD and with HFD after CSD, but not in stressed mice exposed to a continuous HFD treatment. The present work demonstrates that CSD can reduce HFD-induced metabolic dysregulation. Hence, HFD during stress may act beneficially, as comfort food, by decreasing stress-induced metabolic demands.

scholarly journals The effect of calorie intake, fasting, and dietary composition on metabolic health and gut microbiota in mice

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziyi Zhang ◽  
Xiaoyu Chen ◽  
Yuh Jiun Loh ◽  
Xin Yang ◽  
Chenhong Zhang
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Health ◽  
Metabolic Phenotype ◽  
Intermittent Fasting ◽  
High Fat ◽  
Eating Pattern ◽  
Positive Effects ◽  
Normal Chow ◽  
Ad Libitum

Abstract Background Calorie restriction (CR) and intermittent fasting (IF) can promote metabolic health through a process that is partially mediated by gut microbiota modulation. To compare the effects of CR and IF with different dietary structures on metabolic health and the gut microbiota, we performed an experiment in which mice were subjected to a CR or IF regimen and an additional IF control (IFCtrl) group whose total energy intake was not different from that of the CR group was included. Each regimen was included for normal chow and high-fat diet. Results We showed that in normal-chow mice, the IFCtrl regimen had similar positive effects on glucose and lipid metabolism as the CR regimen, but the IF regimen showed almost no influence compared to the outcomes observed in the ad libitum group. IF also resulted in improvements, but the effects were less marked than those associate with CR and IFCtrl when the mice were fed a high-fat diet. Moreover, CR created a stable and unique gut microbial community, while the gut microbiota shaped by IF exhibited dynamic changes in fasting-refeeding cycles. At the end of each cycle, the gut microbiota of the IFCtrl mice was similar to that of the CR mice, and the gut microbiota of the IF mice was similar to that of the ad libitum group. When the abundance of Lactobacillus murinus OTU2 was high, the corresponding metabolic phenotype was improved regardless of eating pattern and dietary structure, which might be one of the key bacterial groups in the gut microbiota that is positively correlated with metabolic amelioration. Conclusion There are interactions among the amount of food intake, the diet structure, and the fasting time on metabolic health. The structure and composition of gut microbiota modified by dietary regimens might contribute to the beneficial effects on the host metabolism.

scholarly journals Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Mrna Levels ◽  
High Fat ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

Yeast β-glucan reduces obesity-associated Bilophila abundance and modulates bile acid metabolism in healthy and high-fat diet mouse models

2021 ◽  
Author(s):  
Sik Yu So ◽  
Qinglong Wu ◽  
Kin Sum Leung ◽  
Zuzanna Maria Kundi ◽  
Tor C Savidge ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Health ◽  
Metabolic Phenotype ◽  
Bile Acid Metabolism ◽  
Microbiota Composition ◽  
High Fat ◽  
Mrna Accumulation ◽  
Gut Microbiota Composition

Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-week dietary supplementation in healthy mice to evaluate effects of different fiber composition (soluble vs particulate Y-BG) and dose (0.1 vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver Cyp7a1 mRNA abundance and bile acid synthesis. These diet-induced responses were notably different when compared to the prebiotic inulin, and included a marked reduction in fecal Bilophila abundance which we demonstrated as translatable to obesity in population-scale American Gut and TwinsUK clinical cohorts. This prompted us to test whether 2% Y-BG maintained metabolic health in mice fed 60% HFD over 13 weeks. Y-BG consistently altered the gut microbiota composition and reduced Bilophila abundance, with trends observed in improvement of metabolic phenotype. Notably, Y-BG improved insulin sensitization and this was associated with enhanced ileal Glpr1r mRNA accumulation and reduced Bilophila abundance. Collectively, our results demonstrate that Y-BG modulates gut microbiota community composition and bile acid signaling, but the dietary regime needs to be optimized to facilitate clinical improvement in metabolic phenotype in an aggressive high-fat diet animal model.

Abstract 037: Role of Pro-opiomelanocortin (POMC) Specific PTP1B in Differential Regulation of Blood Pressure, Liver Lipid Accumulation and Glucose Tolerance in Response to a High Fat Diet

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Nicola Aberdein ◽  
Jussara M do Carmo ◽  
Zhen Wang ◽  
Taolin Fang ◽  
Cecilia P de Lara ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucose Tolerance ◽  
Fat Mass ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Acute Stress ◽  
Liver Lipid ◽  
Liver Weight ◽  
Metabolic Effects ◽  
High Fat

Obese subjects are often resistant to leptin’s metabolic effects although blood pressure (BP) and sympathetic nervous system responses appear to be preserved. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin signaling, may play a role in promoting this selective leptin resistance and causing metabolic dysfunction in obesity. Our previous studies suggest that the chronic BP responses to leptin are mediated via activation of pro-opiomelanocortin (POMC) neurons. The goal of this study was to determine if PTP1B in POMC neurons differentially controls metabolic functions and BP in mice fed a high fat diet (HFD). Male mice with POMC specific PTP1B deletion (POMC/PTP1B -/- ) and littermate controls (PTP1B flox/flox ) were fed a HFD from 6 to 22 wks of age. Baseline BP after 16 weeks of a HFD (95±2 vs. 95±3 mmHg) and BP responses to acute stress (Δ32±0 vs. Δ32±6 mmHg), measured by telemetry, were not different in POMC/PTP1B -/- compared to control mice, respectively. Heart rate (HR) was not different in POMC/PTP1B -/- and control mice during acute stress (699±4 vs. 697±15 bpm, respectively). Total body weight (TBW) and fat mass were reduced at 20 weeks of age in POMC/PTP1B -/- compared to controls (36.7±0.1 vs. 42.0±1 g TBW and 12.7±0.4 vs. 16.1±1.0 g fat mass, respectively). Liver weight of POMC/PTP1B -/- mice was less than in controls, and this was evident even when liver weight was normalized as % of TBW (4.5±0.2 vs. 5.0±0.2 %). POMC/PTP1B -/- males had reduced liver lipid accumulation compared to controls as measured by EchoMRI (0.08±0.03 vs. 0.15±0.03 g/g liver weight). Glucose tolerance was also improved by 46% in POMC/PTP1B -/- compared to controls as measured by AUC, 25856±1683 vs. 47267±5616 mg/dLx120min, respectively. These findings indicate that PTP1B signaling in POMC neurons plays a crucial role in regulating liver lipid accumulation and glucose tolerance but does not appear to mediate changes in BP or BP responses to acute stress in mice fed a high HFD (supported by NHLBI-PO1HL51971 and NIGMS P20GM104357)

scholarly journals Tetrahydro iso-Alpha Acids from Hops Improve Glucose Homeostasis and Reduce Body Weight Gain and Metabolic Endotoxemia in High-Fat Diet-Fed Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33858 ◽  
Author(s):  
Amandine Everard ◽  
Lucie Geurts ◽  
Marie Van Roye ◽  
Nathalie M. Delzenne ◽  
Patrice D. Cani
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
High Fat ◽  
Reduce Body Weight ◽  
Metabolic Endotoxemia

scholarly journals Effect of the Hepatocyte-Specific Deletion of SND1 in Mice on the Liver Insulin Resistance and Acute Liver Failure

2020 ◽  
Author(s):  
Chunyan Zhao ◽  
Xiaoteng Cui ◽  
Baoxin Qian ◽  
Nan Zhang ◽  
Lingbiao Xin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cholesterol Level ◽  
Hepatic Steatosis ◽  
Glucose Homeostasis ◽  
Hepatic Failure ◽  
High Fat Diet ◽  
High Fat ◽  
Specific Deletion

Abstract Background: The multifunctional protein SND1 was reported to be involved in a variety of biological processes, such as cell cycle, proliferation or lipogenesis. We previously proposed that global-expressed SND1 in vivo is likely to be a key regulator for ameliorating HFD-induced hepatic steatosis and systemic insulin resistance. Herein, we are very interested in investigating further whether the hepatocyte-specific deletion of SND1 affects the insulin resistance or acute liver failure (ALF) of mice.Methods: By using Cre-loxP technique, we constructed conditional knockout (LKO) mice of SND1 driven by albumin in hepatocytes and analyze the changes of glucose homeostasis, cholesterol level, hepatic steatosis and hepatic failure under the treatment of high-fat diet (HFD) or upon the simulation of Lipopolysaccharide/galactosamine (LPS/GalN).Results: No difference for the body weight, liver weight, and cholesterol level was detected. Furthermore, we did not observe the alteration of glucose homeostasis in SND1 hepatic knockout mice on either chow diet or high-fat diet. Besides, hepatocyte-specific deletion of SND1 failed to influence the hepatic failure of mice induced by LPS/GalN.Conclusions: These findings suggest that hepatic SND1, independently, is insufficient for changing glucose homeostasis, hepatic lipid accumulation and inflammation. The synergistic action of multiple organs may contribute to the role of SND1 in insulin sensitivity or inflammatory response.

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