scholarly journals Gabra5LHA Mediate Astrocytic GABA-induced Obesity via Decreasing Energy Expenditure

2021 ◽  
Author(s):  
C. Justin Lee ◽  
Moonsun Sa ◽  
Eun-Seon Yoo ◽  
Wuhyun Koh ◽  
Mingu Gordon Park ◽  
...  
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Energy Expenditure ◽  
Mouse Model ◽  
Gene Silencing ◽  
Selective Inhibition ◽  
Hypothalamic Area ◽  
Adipose Tissues ◽  
Diet Induced Obesity ◽  
Distinct Subpopulation

The lateral hypothalamic area (LHA) regulates food intake and energy expenditure. Although LHA neurons innervate adipose tissues, the identity of neurons that regulate fat is undefined. Here we identify that Gabra5-positive neurons in LHA (Gabra5LHA) polysynaptically project to brown and white adipose tissues in the periphery. Gabra5LHA are a distinct subpopulation of GABAergic neurons and show decreased pacemaker firing in diet-induced obesity (DIO) mouse model. Gene silencing of Gabra5 in LHA decreases weight gain, whereas chemogenetic inhibition of LHA suppresses energy expenditure and increases weight gain. In DIO mouse model, Gabra5LHA are tonically inhibited by nearby reactive astrocytes releasing GABA, which is synthesized by MAOB. Administration of a MAOB inhibitor, KDS2010 reduces weight gain significantly without affecting food intake, which is recapitulated by gene-silencing of astrocytic MAOB in LHA. We propose that firing of Gabra5LHA facilitates energy expenditure and selective inhibition of astrocytic GABA is a molecular target for treating obesity.

scholarly journals Susceptibility to diet induced obesity at thermoneutral conditions is independent of UCP1

2021 ◽  
Author(s):  
Sebastian Dieckmann ◽  
Akim Strohmeyer ◽  
Monja Willershaeuser ◽  
Stefanie Maurer ◽  
Wolfgang Wurst ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Knockout Mice ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Exon 2 ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Knockout Model

Objective Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of Exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. Methods UCP1 knockout and wildtype mice were housed at 30°C and fed a control diet for 4-weeks followed by 8-weeks of high-fat diet. Body weight and food intake were monitored continuously over the course of the study and indirect calorimetry was used to determine energy expenditure during both feeding periods. Results Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake and energy expenditure were not affected by deletion of UCP1 gene function during both feeding periods. Conclusion Conclusively, we show that UCP1 does not protect against diet-induced obesity at thermoneutrality. Further we introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages.

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

Diabetologia ◽  
2013 ◽  
Vol 56 (10) ◽  
pp. 2297-2307 ◽  
Author(s):  
Y.-Y. Fu ◽  
M. Zhang ◽  
N. Turner ◽  
L.-N. Zhang ◽  
T.-C. Dong ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Diet Induced Obesity ◽  
Chemical Uncoupler

scholarly journals Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5855-5864 ◽  
Author(s):  
Jonathan D. Roth ◽  
Heather Hughes ◽  
Eric Kendall ◽  
Alain D. Baron ◽  
Christen M. Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Lean Tissue ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Cell Hormone

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 μg/kg·d, 22d) reduced food intake and slowed weight gain: approximately 10% (P < 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P < 0.05). Whereas PF decreased lean tissue (P < 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean ± se, 0.82 ± 0.0, 0.81 ± 0.0, respectively; P < 0.05) similar to VEH (0.84 ± 0.01). Energy expenditure (EE mean ± se) tended to be reduced by PF (5.67 ± 0.1 kcal/h·kg) and maintained by amylin (5.86 ± 0.1 kcal/h·kg) relative to VEH (5.77 ± 0.0 kcal/h·kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09 kcal/·kg; P < 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07 kcal/h·kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P < 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P < 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

Extract of Irish potatoes (Solanum tuberosumL.) decreases body weight gain and adiposity and improves glucose control in the mouse model of diet-induced obesity

2014 ◽  
Vol 58 (11) ◽  
pp. 2235-2238 ◽  
Author(s):  
Stan Kubow ◽  
Luc Hobson ◽  
Michèle M. Iskandar ◽  
Kebba Sabally ◽  
Danielle J. Donnelly ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Mouse Model ◽  
Glucose Control ◽  
Body Weight Gain ◽  
Diet Induced Obesity

scholarly journals SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4542-4549 ◽  
Author(s):  
Bassil M. Kublaoui ◽  
J. Lloyd Holder ◽  
Kristen P. Tolson ◽  
Terry Gemelli ◽  
Andrew R. Zinn
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Transgenic Mice ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Enhanced Sensitivity ◽  
Diet Induced Obesity ◽  
Melanocortin 4 Receptor ◽  
Obesity In Mice

Single-minded 1 (SIM1) mutations are associated with obesity in mice and humans. Haploinsufficiency of mouse Sim1 causes hyperphagic obesity with increased linear growth and enhanced sensitivity to a high-fat diet, a phenotype similar to that of agouti yellow and melanocortin 4 receptor knockout mice. To investigate the effects of increased Sim1 dosage, we generated transgenic mice that overexpress human SIM1 and examined their phenotype. Compared with wild-type mice, SIM1 transgenic mice had no obvious phenotype on a low-fat chow diet but were resistant to diet-induced obesity on a high-fat diet due to reduced food intake with no change in energy expenditure. The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated. Our results indicate that the melanocortin 4 receptor signals through Sim1 or its transcriptional targets in controlling food intake but not energy expenditure.

A specific dose of grape seed-derived proanthocyanidins to inhibit body weight gain limits food intake and increases energy expenditure in rats

2016 ◽  
Vol 56 (4) ◽  
pp. 1629-1636 ◽  
Author(s):  
Joan Serrano ◽  
Àngela Casanova-Martí ◽  
Andreu Gual ◽  
Anna Maria Pérez-Vendrell ◽  
M. Teresa Blay ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Grape Seed

scholarly journals Kappa-Carrageenan Inhibited the High-Fat-Diet-Induced Obesity Through Up-Regulating the Hepatic Sirt1 Gene Expression

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 503-503
Author(s):  
Zhiji Huang ◽  
Yafang Ma ◽  
Chunbao Li
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Energy Intake ◽  
High Fat Diet ◽  
The Body ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Sirt1 Gene ◽  
Kappa Carrageenan

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake.  The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)

scholarly journals STAT3 but Not ERK2 Is a Crucial Mediator Against Diet-Induced Obesity via VMH Neurons

2021 ◽  
Author(s):  
Gabriel Henrique Marques Gonçalves ◽  
Sabrina Mara Tristão ◽  
Rafaella Eduarda Volpi ◽  
Gislaine Almeida-Pereira ◽  
Beatriz de Carvalho Borges ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Specific Pattern ◽  
Conditional Knockout ◽  
Steroidogenic Factor 1 ◽  
Diet Induced Obesity ◽  
Affect Body Weight

Leptin plays an important role in the protection against diet-induced obesity (DIO) by its actions in ventromedial hypothalamic (VMH) neurons. However, little is known about the intracellular mechanisms involved in these effects. To assess the role of the STAT3 and ERK2 signaling in neurons that express the steroidogenic factor 1 (SF1) in the VMH on energy homeostasis, we used cre-lox technology to generate male and female mice with specific disruption of STAT3 or ERK2 in SF1 neurons of the VMH. We demonstrated that the conditional knockout of STAT3 in SF1 neurons of the VMH did not affect body weight, food intake, energy expenditure and glucose homeostasis in animals on regular chow. However, when challenged with high-fat diet (HFD), loss of STAT3 in SF1 neurons caused a significant increase in body weight, food intake and energy efficiency that was more remarkable in females which also showed a decrease in energy expenditure. In contrast, deletion of ERK2 in SF1 neurons of VMH did not have any impact on energy homeostasis in both regular diet and HFD conditions. In conclusion, STAT3 but not ERK2 signaling in SF1 neurons of VMH plays a crucial role to protect against DIO in a sex-specific pattern.

scholarly journals Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in mice

2018 ◽  
Author(s):  
Vruti Patel ◽  
Guillaume Bidault ◽  
Joseph E. Chambers ◽  
Stefania Carobbio ◽  
Angharad J. T. Everden ◽  
...  
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Standard Diet ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Caloric Excess ◽  
Deficient Mice

AbstractPhosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.

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