Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Estrogen Drives Melanocortin Neurons To Reduce Sedentary Behavior

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE141434 | GEO | 2021/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Functional expression of melanocortin 4 receptor in monocytes to suppress aortic aneurysm and atherosclerosis in mice

Project description:Melanocortin-4 receptor (MC4R) mediates most anorectic leptin response effects to an agonist, α-melanocyte-stimulating hormone (α-MSH). MC4R mutations are considered to be the main cause of monogenetic obesity in humans. It has been reported that the activity loss of MC4R gene increases body mass index and cardiovascular event risk in humans. This study aimed to investigate our hypothesis that MC4R signaling directly modulates vascular functions and that MC4R signaling loss leads to vascular diseases, such as vascular vulnerability and abdominal aortic aneurysm (AAA). To understand the molecular mechanism by which myeloid MC4R inhibits atherosclerosis and Ang II-induced AAA in mice, we first conducted a microarray analysis of LysM (+);MC4RTB/TB and MC4RTB/TB mouse primary BM-derived macrophages.

2022-03-21 | GSE198975 | GEO

Estrogen Drives Melanocortin Neurons To Reduce Sedentary Behavior

Project description:Estrogen Drives Melanocortin Neurons To Reduce Sedentary Behavior

| PRJNA593491 | ENA

A neural basis for melanocortin-4 receptor-regulated appetite.

Project description:Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVH(MC4R) neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVH(MC4R)→lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVH(MC4R)→LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development.

2016-12-03 | GSE90809 | GEO

Estrogen Drives Melanocortin Signaling to Increase Spontaneous Activity

Project description:Estrogen Drives Melanocortin Signaling to Increase Spontaneous Activity

| PRJNA751050 | ENA

A Brain-Melanocortin-Vagus axis mediates adipose tissue expansion independently of energy intake.

Project description:The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing Sympathetic Nervous input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here we demonstrate that obesogenic signals, including reduction of brain-melanocortin signaling or high-fat feeding, actively promote fat mass gain independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. These signals promote adipose tissue expansion by activating lipogenic program and adipocyte and endothelial cell proliferation independently of insulin action or the sympathetic tone to adipose tissue. These data reveal a novel physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity.

2019-04-18 | GSE128383 | GEO

Forebrain neuronal Smc3 regulates weight and metabolic parameters associated with regulation of hypothalamic Melanocortin 4 receptor

Project description:SMC3 is a major component of the cohesin complex that regulates higher-order chromatin organization and gene expression. Mutations in SMC3 gene are found in patients with Cornelia de Lange syndrome (CdLs). This syndrome is characterized by intellectual disabilities, behavioral patterns as self-injury, as well as metabolic dysregulation. Nonetheless, little is known about the role of neuronal SMC3 in gene expression and physiology in adulthood. This study determined the role of SMC3 in adulthood brain, by knocking out Smc3 specifically in adulthood forebrain excitatory neurons. Neuron-specific SMC3 knockout mice displayed a very strong metabolic phenotype in both male and female mice, including a robust overweight phenotype, loss of muscle mass, increased food consumption, lower respiratory exchange ratio, lower energy expenditure and hormonal changes. The hypothalamus of these mice displayed dysregulated morphology and RNA-seq in the hypothalamus reveals dysregulation in multiple cellular pathways, including decrease of Melanocortin 4 receptor (Mc4r) expression level, a main regulator of appetite. Treatment of these mice with Setmelanotide, a MC4r agonist, induced a decrease of weight and food consumption in these mice. Therefore, we have identified specific and reversable metabolic parameters that are regulated by neuronal Smc3 in adulthood.

2024-01-04 | GSE252366 | GEO

Forebrain neuronal Smc3 regulates weight and metabolic parameters partly through regulation of hypothalamic Melanocortin 4 receptor

Project description:SMC3 is a major component of cohesin complex that regulates higher-order chromatin organization and gene expression. Mutations in SMC3 gene are found in patients with Cornelia de Lange syndrome (CdLs). This syndrome is characterized by intellectual disabilities, behavioral patterns as self-injury, as well as metabolic dysregulation. Nonetheless, little is known about the role of neuronal SMC3 in gene expression and physiology especially in adulthood. This study determined the role of SMC3 in adulthood brain, by knocking out Smc3 specifically in adulthood forebrain excitatory neurons. Neuron-specific SMC3 knockout mice displayed a very strong metabolic phenotype in both male and female mice, including a robust overweight phenotype, loss of muscle mass, increased food consumption, lower respiratory exchange ratio, lower energy expenditure and hormonal changes. The hypothalamus of these mice displayed dysregulated morphology and RNA-seq in the hypothalamus reveals dysregulation in multiple cellular pathways, including decrease of Melanocortin 4 receptor (Mc4r) expression level , a main regulator of appetite. Treatment of these mice with Setmelanotide, a MC4r agonist, induced a decrease of weight and food consumption in these mice. Therefore, we have identified specific metabolic pathways that are regulated by Smc3 in forebrain neurons, and specific mechanisms that are involved.

2023-09-18 | GSE243287 | GEO

Loss of the Melanocortin 4 Receptor in mice causes dilated cardiomyopathy.

Project description:Deletion of the melanocortin-4 receptor in mice causes dilated cardiomyopathy that is independent of obesity.

2018-05-01 | GSE98439 | GEO

Transcription profiling of pig liver and fat tissues during fasting from animals MC4R D298N variant

Project description:Transcriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight and backfat and increased serum concentrations of non-esterified fatty acid and urea. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE, q value less than 0.05). MC4R genotype did not affect gene expression, body weight, backfat depth, and any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that both liver and fat down-regulated energetically costly processes such as lipid and steroid synthesis and up-regulated efficient energy utilization pathways. Fasting increased expression of genes in involved in glucose sparing pathways in liver and extracellular matrix pathways in adipose tissue. Within the DE genes, transcription factors (TF) that regulate many DE genes were identified, confirming the involvement of TF that are known to regulate fasting response and implicating additional TF that are not known to be involved in energy homeostatic responses. Interestingly, estrogen receptor 1 transcriptionally controls fasting induced genes in fat that are involved in cell matrix morphogenesis. Our findings indicate a transcriptional response to fasting in two key metabolic tissues of pigs that was corroborated by changes in blood metabolites; and involvement of novel putative transcriptional regulators in the immediate adaptive response to fasting. Experiment Overall Design: Gilts (n=24; 12 wildtype and 12 homozygous for D298N) were either fed ad libitum or fasted for 3 days in a completely randomized complete block design with a 2x2 factorial treatment structure.

2009-04-25 | E-GEOD-13528 | biostudies-arrayexpress

Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor

Project description:In this study we investigated the effect of normal chow (0 % cholesterol) or a semisynthetic diet (high sugar, 0.02 % cholesterol) fed to mice lacking either Mc4r, Ldlr or both and wildtype animals (total of 4 genotypes) by generating an expression profile of their livers after 6 months by RNA sequencing.

2017-03-08 | GSE87743 | 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