Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE148599 | GEO | 2020/10/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Project description:Hypothalamic REV-ERBs Control Circadian Food Intake and Leptin Sensitivity

| PRJNA625268 | ENA

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

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

| PRJNA625110 | ENA

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

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

| PRJNA625265 | ENA

Gut Microbe-Targeted Choline Trimethylamine Lyase Inhibitors Improves Obesity Via Rewiring of Host Circadian Rhythms.

Project description:The increasing prevalence of obesity and related metabolic disorders represents a growing public health concern. Despite advances in other areas of medicine, a safe and effective drug treatment for obesity has been elusive. Obesity has repeatedly been linked to reorganization of the gut microbiome 1-4 , yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here we show that gut microbe-targeted inhibition of the metaorganismal trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (ob/ob). Selective small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not significantly reduce food intake, but instead is associated with beneficial remodeling of the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. Leveraging untargeted metabolomics we discovered that CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. Collectively, this study underscores the close relationship between microbe and host metabolism, and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors can have profound effects on host energy metabolism, and have untapped potential as anti-obesity therapeutics.

2021-03-31 | GSE157925 | GEO

Early Leptin Intervention Reverses Perturbed Energy Balance Regulating Hypothalamic Neuropeptides in the Pre- and Postnatal Calorie Restricted Offspring

Project description:Pre- and postnatal calorie restriction is associated with postnatal growth restriction, reduced circulating leptin concentrations and perturbed energy balance. Hypothalamic regulation of energy balance demonstrates enhanced orexigenic (NPY, AgRP) and diminished anorexigenic (POMC, CART) neuropeptide expression (PN21) setting the stage for subsequent development of obesity. Leptin replenishment during the early postnatal period (PN2-PN8) led to reversing the hypothalamic orexigenic:anorexigenic neuropeptide ratio at PN21 by only reducing the orexigenic (NPY, AgRP) without affecting the anorexigenic (POMC, CART) neuropeptide expression. This hypothalamic effect was mediated via enhanced leptin receptor (ObRb) signaling that involved increased pSTAT3 but reduced PTP1B. This was further confirmed by an increase in body weight at PN21 in response to intracerebroventricular administration of antisense ObRb oligonucleotides (PN2-PN8). The change in the hypothalamic neuropeptide balance in response to leptin administration caused increased oxygen consumption, carbon dioxide production and physical activity which resulted in increased milk intake (PN14) with no change in body weight. This is in contrast to the reduction in milk intake with no effect on energy expenditure and physical activity observed in controls. We conclude that pre- and postnatal calorie restriction perturbs hypothalamic neuropeptide regulation of energy balance setting the stage for hyperphagia and reduced energy expenditure, hallmarks of obesity. Leptin in turn reverses this phenotype by increasing hypothalamic ObRb signaling (sensitivity) and affecting only the orexigenic arm of the neuropeptide balance.

2014-12-31 | GSE55384 | GEO

Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits

Project description:The paraventricular hypothalamus (PVH) is crucial for food intake control, yet the presynaptic mechanisms underlying PVH neurons remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 results in hyperphagic obesity in mice. RUVBL2-expressing neurons in the PVH (PVHRUVBL2) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVHRUVBL2 neurons form the synaptic connections with POMC and AgRP neurons in the ARC. PVH RUVBL2 KO impairs the excitatory synaptic transmission by reducing presynaptic boutons and synaptic vesicles near active zone. Finally, RUVBL2 overexpression in the PVH suppresses food intake and protects against diet induced obesity. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulation of synaptic plasticity could be an effective way to curb appetite and obesity.

2024-10-02 | GSE249791 | GEO

Diet induced obesity is independent of metabolic endotoxemia, Tlr4 signalling and hypothalamic inflammation

Project description:A number of studies have proposed that excess food intake, particularly of high fat diets arise due dysregulation of homeostatic mechanisms regulating neuroendocrine control of appetite and energy balance. Current dogma suggests high fat diets invoke hypothalamic inflammation which reduces hypothalamic sensitivity to metabolic and hormonal cues of conveying peripheral status of energy balance, such as leptin and insulin. A hypothesis for the mechanism leading to hypothalamic inflammation is based on high fat diet mediated changes in gut microbiota which are then proposed to increase circulating levels of lipopolysaccharide (LPS). This in turn activates a hypothalamic inflammatory response via the toll-like receptor (TLR4) and CD14. The aim of this study was to determine hypothalamic gene expression in response to long term feeding of a high fat diet, taking into account the importance of using a control diet with a similar composition and balanced for sucrose content.

2018-10-23 | E-MTAB-6929 | biostudies-arrayexpress

Amygdala NPY circuits are critical for the development of accelerated obesity under chronic stress

Project description:Neuropeptide Y (NPY) exerts powerful feeding related functions in the hypothalamus. However, NPY is also present in extra-hypothalamic nuclei, however their influence on energy homeostasis is unclear. Here we uncover a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie dense food with NPY neurons in the central amygdala (CeA) being responsible for an exacerbated response to a combined stress and high fat diet intervention. CeA NPY neuron specific Npy overexpression mimics the obese phenotype seen in a stress/HFD model, which is prevented by the selective ablation of Npy. Using food intake and energy expenditure (EE) as readout we demonstrate that selective activation of CeA NPY neurons results in increased food intake and a decrease in EE, which requires the presence of NPY. Mechanistically it is the diminished insulin signalling capacity on CeA NPY neurons under stress combined with HFD conditions that leads to the exaggerated development of obesity.

2019-03-31 | GSE128413 | GEO

The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue

Project description:Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesized that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discovered that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impaired BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This was associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic.

2021-07-19 | GSE178366 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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