Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protection against overfeeding-induced weight gain in mice is preserved in obesity but does not require FGF21 or MC4R

ABSTRACT: Experimental overfeeding triggers homeostatic compensatory mechanisms that counteract weight gain. Here, we utilized intragastric overfeeding in mice to investigate the physiological and molecular responses to forced weight gain. Both lean and diet-induced obese (DIO) mice exhibited a potent and prolonged lowering of voluntary food intake following overfeeding-induced weight gain. Although overfeeding resulted in a marked increase in circulating fibroblast growth factor 21 (FGF21), experiments with FGF21 knockout (KO) mice demonstrated that FGF21 is dispensable for the homeostatic defense against experimental weight gain. Targeted proteomics unveiled novel circulating factors linked to overfeeding, including the protease legumain (LGMN). Notably, administration of recombinant LGMN lowered body weight and food intake in DIO mice. The protection against weight gain was also associated with reduced vascularization in the hypothalamus and sustained reductions in transcript levels of the orexigenic neuropeptides, Npy and AgRP, suggesting a role of hypothalamic signaling in the homeostatic recovery from overfeeding. Overfeeding of melanocortin 4 receptor (MC4R) KO mice showed that these mice can suppress voluntary food intake and counteract the enforced weight gain, although their rate of weight recovery is impaired. Collectively, these findings demonstrate that the defense against overfeeding-induced weight gain remains intact in obesity and involves mechanisms independent of both FGF21 and MC4R.

ORGANISM(S): Mus musculus

PROVIDER: GSE247825 | GEO | 2024/01/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The role of FGF21 in aging and aging-related diseases

Project description:Aging and aging-related diseases represent an increasing burden on modern society. Thus, drugs that retard the aging process are highly desirable. Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity and blocks somatic growth. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting AMP kinase or mTOR signaling or NAD metabolism. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used as a hormone therapy to extend lifespan. Liver, epididymal fat and gastrocnemius muscle RNA expression profiles were compared between C57Bl/6J ad libitum, fasted, and calorically restricted mice, as well as between FGF-21 transgenic and their wild-type C57Bl/6J controls.

2012-10-18 | E-GEOD-39313 | biostudies-arrayexpress

Hypothalamic REV-ERBs Control Circadian Food Intake and Leptin Sensitivity [RNA-seq]

Project description:Obesity occurs when energy expenditure is outweighed by food intake. Tuberal hypothalamic nuclei, including the arcuate nucleus (ARC), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH), regulate feeding amount as well as energy expenditure. Here we report that mice lacking circadian nuclear receptors REV-ERBa and b in the tuberal hypothalamus (HDKO) gain excessive weight on an obesogenic diet due both to decreased energy expenditure and increased food consumption during the light phase. Moreover, rebound food intake after fasting is markedly increased in HDKO mice. Integrative transcriptomic and cistromic analyses revealed that such disruption in feeding behavior is due to perturbed REV-ERB-dependent leptin signaling in the ARC. Indeed, in vivo leptin sensitivity is impaired in HDKO mice on an obesogenic diet in a circadian manner. Thus, REV-ERBs play a crucial role in hypothalamic regulation of food intake and circadian leptin sensitivity in diet-induced obesity.

2020-10-11 | GSE148641 | GEO

Hypothalamic REV-ERBs Control Circadian Food Intake and Leptin Sensitivity [ChIP-seq]

2020-10-11 | GSE148599 | GEO

RNA-Seq analysis on the liver of mice treated with high-fat diet and liraglutide

Project description:GLP-1 based diabetes drugs are effective to reduce hepatic lipid accumulation beyong glycemic control. As GLP-1 receptor (GLP-1R) is not expressed in hepatocytes, the mechanism behind the beneficial effects of GLP-1 based drugs on the liver remained elusive. Several studies have shown that the expression of hepatic fibroblast growth factor 21 (FGF21) can be stimulated by GLP-1-based drugs. Therefore, the present study aimed to assess such stimulation in mice and in mouse primary hepatocytes, determine whether hepatic FGF21 mediates functions of the GLP-1R agonist liraglutide, and to explore the potential mechanisms of liraglutide regulating the expression of FGF21. In high-fat diet induced obese mice, we observed hepatic and plasma FGF21 elevation, improved glucose disposal, and reduced plasma triglyceride levels by liraglutide treatment. Moreover, RNA-sequencing on the liver suggested that Fgf21 was the most upregulated gene after liraglutide treatment. In liver-specific FGF21 knock-out mice on high-fat and high-fructose diet, the body-weight gain attenuation and lipid homeostatic effects of liraglutide was lost or significantly reduced. These studies implied that hepatic FGF21 was the critical mediator of liraglutide-induced metabolic improvement.

2021-03-16 | GSE168937 | GEO

Estrogen Drives Melanocortin Neurons To Reduce Sedentary Behavior

Project description:Estrogen depletion in both rodents and humans leads to inactivity, unhealthy fat accumulation, and metabolic syndrome, underscoring the conserved metabolic benefits of estrogen signaling that inevitably decline with aging. Here, we uncover a hypothalamic node that integrates estrogen and melanocortin-4 receptor (MC4R) signaling to drive episodic bursts in activity prior to ovulation. Skirting the estrogen-dependent gating of this node by CRISPR activation of Mc4r reduces sedentary behavior long-term in both males and females. Our findings expand the impact of MC4R signaling beyond food intake regulation and rationalize reported sex-differences in melanocortin signaling including increased disease severity for women with MC4R-insuffciency. This newly identified hormone-dependent activity node illustrates the potency of estrogen in maintaining an active lifestyle.

2021-03-01 | GSE141434 | GEO

The role of FGF21 in aging and aging-related diseases

2012-10-18 | GSE39313 | GEO

K.Woollard_Aglient

Project description:Human monocytes are phagocytic leucocytes which circulate in the peripheral blood and play important roles in immunity and inflammation. They also represent circulating M-^QmetabolicM-^R sentinels in plasma, uptake lipids following food intake, and contribute to atherosclerotic plaque formation. We therefore investigated their homeostatic responses to food intake in vivo and to determine the response of human monocytes to food intake. We isolated monocyte subsets from the blood of healthy volunteers one hour before and four hours after a western type lunch.

2012-09-19 | E-MEXP-3377 | biostudies-arrayexpress

Targeting Clic1 for the Treatment of Obesity: A Novel Therapeutic Strategy to Reduce Food Intake and Body Weight

Project description:Overconsumption of energy-rich food is a key driver of the obesity epidemic. However, the neural circuits that regulate food overconsumption are highly complex and many molecular components of these circuits remain unknown. Our recent studies attribute a novel role of Clic1 as a driver of food intake and overconsumption. Clic1 is expressed in the arcuate nucleus of the hypothalamus and expression specifically increases in Agrp/Npy neurons in the fasted state. Importantly, Clic1 exists in two forms and fasting induces a transformation from the predominant soluble enzymatic form to the membrane-associated ion channel form. Clic1KO mice eat significantly less and have a lower body weight than WT littermates when either fed chow or high fat diet. Furthermore, pharmacological inhibition of Clic1 inhibition results in suppression of food intake and promotes highly efficacious weight loss in obese mice.

2023-07-31 | GSE229799 | GEO

Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones

Project description:Fibroblast growth factor-21 (FGF21) is a circulating hepatokine that beneficially affects carbohydrate and lipid metabolism. Here we report that FGF21 is also an inducible, fed-state autocrine factor in adipose tissue that functions in a feed-forward loop to regulate the activity of peroxisome proliferator-activated receptor γ (PPARγ), a master transcriptional regulator of adipogenesis. FGF21-knockout (KO) mice display defects in PPARγ signaling including decreased body fat and attenuation of PPARγ-dependent gene expression. Moreover, FGF21-KO mice are refratory to both the beneficial, insulin-sensitizing effects and the detrimental weight gain and edema side effects of the PPARγ agonist rosiglitazone. This loss of function in FGF21-KO mice is coincident with a marked increase in the sumoylation of PPARγ, which reduces its transcriptional activity. Adding back FGF21 prevents sumoylation and restores PPARγ activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPARγ.

2020-01-23 | GSE33684 | GEO

Hepatic gene expression profiling reveals key pathways involved in leptin mediated weight loss in ob/ob mice.

Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison

2010-11-10 | GSE20878 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data