Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Isolating Independent Effects of Diet/Energy Balance and Body Weight on Behavior and Metabolic Health

ABSTRACT: Associated with numerous metabolic and behavioral abnormalities, obesity is classified by metrics reliant on body weight (such as body mass index). However, overnutrition is the common cause of obesity, and may independently contribute to these obesity-related abnormalities. The goal of this study is to isolate ‘diet/energy balance’ effects independent from ‘body weight’ effects on various metabolic and behavioral parameters using the Diet Switch feeding paradigm in mice. [We conducted] unbiased gene expression analysis of the nutrient-sensing circumventricular hypothalamus [using RNA-seq]. Remarkably, only two genes responded to diet/energy balance (neuropeptide y [npy] and agouti-related peptide [agrp]), while others were related only to body weight. Furthermore, linear regression models revealed that npy and agrp showed similar modifiability by diet/energy balance and body weight compared to electroencephalographic-measured sleep/wake behavior.

ORGANISM(S): Mus musculus

PROVIDER: GSE104709 | GEO | 2018/05/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Comparative transcriptomic analyses of developing melanocortin neurons reveal new regulators for the anorexigenic neuron identity

Project description:Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive.We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in E15.5 mice embryos. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons.Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression nor energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.

2020-03-12 | GSE146816 | GEO

Transcription Factors Dlx1 and Otp Segregate the Identity of Orexigenic/Anti-thermogenic- and Growth Promoting-Neurons in the Arcuate Nucleus

Project description:The hypothalamic arcuate nucleus contains multiple types of neurons controlling critical physiological processes. However, the gene regulatory network directing their development remains rudimentary. Here we report that two transcription factors Otp and Dlx1 segregate the identity of orexigenic/anti-thermogenic NPY/AgRP- and growth-promoting GHRH-neurons in the developing arcuate nucleus. Otp-null and Dlx1-null mice lose NPY/AgRP and GHRH expression, respectively. Dlx1-null mice also show enhanced expression of Otp/NPY/AgRP, which is normalized in Dlx1;Otp-double mutant mice. Correspondingly, Dlx1-null mice exhibit decreased growth, lower body temperature and increased feeding. Furthermore, our genome-wide studies identify Otp as a negative target gene of Dlx1. Therefore, Otp is critical for NPY/AgRP-neuronal development, while Dlx1 promotes GHRH-neuronal development and antagonizes NPY/AgRP-neuronal development. These results identify a mechanism for segregating the identity of two functionally related neurons, and the Dlx1-Otp axis likely contributes to coordinating energy balance and growth by maintaining a proper ratio of NPY/AgRP- to GHRH-neurons.

2018-05-31 | GSE104372 | GEO

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

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

Project description:The arcuate nucleus of the hypothalamus (ARH) is one key structure controlling energy homeostasis. While it has been shown that the biogenic amines dopamine and serotonin modulate food intake controlling NPY/AgRP and/or POMC neurons in the ARH, the neural substrates that mediate the effect of noradrenaline (NA) on energy homeostasis remain elusive. By electrophysiological recordings and cell type-specific transcriptomics we show that the main neuronal populations in the ARH, NPY/AgRP and POMC neurons express a combination of excitatory and inhibitory adrenergic receptors (ARs). Surprisingly, NA had a clear differential effect on these neurons. Activation of NPY/AgRP neurons is mediated by _1A - and _- ARs, while POMC neurons are inhibited via _2A ARs. Collectively, our data indicate an orexigenic influence of NA on the ARH circuitry that controls energy balance

2017-10-26 | GSE106188 | GEO

Cell type transcriptomics of hypothalamic energy-sensing neuron responses to fasting

Project description:AGRP neurons are a hypothalamic population that senses physiological energy deficit and consequently increases appetite. Molecular and cellular processes for energy-sensing and elevated neuronal output are critical for understanding the central nervous system response to energy deficit states, such as during weight-loss. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss but, in adult mice, this has been limited by technical challenges. We report high-quality gene expression profiles of AGRP neurons under well-fed and energy deficit states. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite. This data newly identifies cell type-selective involvement of signaling pathways, ion channels, neuropeptides, and G-protein coupled receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. Examination of 2 different neuronal cell types under 2 conditions.

2015-09-02 | E-GEOD-68177 | biostudies-arrayexpress

Cancer anorexia: the role of serotonin in hypothalamic resistance of the neuropeptide Y system [A286_GEO_LLM]

Project description:Anorexia is a common symptom among cancer patients and contributes to malnutrition and insufficient food intake. In cancer-induced anorexia, food intake regulation in the hypothalamus appears to be impaired. A negative energy balance persists and accelerates muscle wasting and malnutrition. Moreover, it strongly affects mortality and survival in these patients. Here, we show that the neuropeptide Y system (NPY) appears to fail to respond adequately to changes in energy balance during cancer cachexia. In addition, we investigate the connection between serotonin and NPY release in hypothalamic cell lines. Lewis Lung tumour cells were intramuscularly inoculated 6w old male C57BL/6 mice. Body weight and food intake were measured 3 times a week. On day 10, 14 and 17 hypothalamus was dissected and used for gene expression profiling.

2014-10-31 | E-GEOD-57188 | biostudies-arrayexpress

Characterization of a new selective glucocorticoid receptor modulator with anorexigenic activity

Project description:Obesity, a worldwide epidemic, leads to various metabolic disorders threatening human health. In response to stress or fasting, glucocorticoid (GC) levels are elevated to promote food intake. This involves GC-induced expression of the orexigenic neuropeptides in agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) via the GC receptor (GR). Here, we report a selective GR modulator (SGRM) that suppresses GR-induced transcription of genes with non-classical glucocorticoid response elements (GREs) such as Agrp-GRE, but not with classical GREs, and via this way may serve as a novel anti-obesity agent. We have identified a novel SGRM, 2-O-trans-p-coumaroylalphitolic acid (Zj7), a triterpenoid extracted from the Ziziphus jujube plant, that selectively suppresses GR transcriptional activity in Agrp-GRE without affecting classical GREs. Zj7 reduces the expression of orexigenic genes in the ARC and exerts a significant anorexigenic effect with weight loss and increased energy expenditure in both high-fat diet-induced obese and genetically obese db/db mouse models. Transcriptome analysis showed that Zj7 represses the expression of a group of orexigenic genes including Agrp and Npy induced by the synthetic GR ligand dexamethasone (Dex) in the hypothalamus. Overall, our studies demonstrate that selectively targeting the orexigenic action of GR in AgRP neurons is a promising approach for the treatment of metabolic disorders with fewer side effects.

2024-04-10 | GSE260739 | GEO

Cell type transcriptomics of hypothalamic energy-sensing neuron responses to fasting

2015-09-02 | GSE68177 | GEO

Liver phosphoproteomics in response to AgRP activated neurons in the presence/absence of NPY

Project description:Autophagy represents a key regulator of aging and metabolism upon cell autonomous sensing of energy deprivation. We find that fasting in mice activates autophagy in liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators and promotes ß-oxidation in the liver. AgRP neuron dependent induction of liver autophagy relies on NPY expression in these neurons. AgRP neuron projections in the paraventricular nucleus of the hypothalamus (PVH) and the lateral hypothalamus (LHA) mediate AgRP neuron-dependent control of liver autophagy. Conversely, inhibiting AgRP neurons during energy deprivation abrogates induction of hepatic autophagy and re-wiring of metabolism. Finally, AgRP neuron activation increases circulating corticosterone concentrations, and reduction of hepatic glucocorticoid receptor expression attenuates AgRP neuron-dependent activation of hepatic autophagy. Collectively, our study reveals a fundamental regulatory principle of non-cell autonomous control of liver autophagy in control of metabolic adaptation during nutrient deprivation.

2023-04-18 | PXD029247 | Pride

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