Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline
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PROVIDER: PRJNA415839 | ENA |
REPOSITORIES: ENA
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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
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
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
Project description: Not available
| S-EPMC5478265 | biostudies-literature
Project description:Agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combined non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons allowing to compare metabolic responses in mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. These experiments revealed that food intake is regulated by the additive effect of AgRP-neuron activation and POMC-neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated versus simultaneous regulation of AgRP and POMC neurons. We identified a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus (PVH), where activated AgRP- and inhibited POMC neurons synergize to promote food consumption and activate neurons in the nucleus tractus solitarii (NTS). We then performed single-nuclei RNA sequencing to define the molecular nature of Fos+ cells in the posterior NTS/AP area that respond to simultaneous chemogenetic intervention over AgRP and POMC neurons and identified TH+ neurons as candidates for receiving neuronal inputs initiated by the simultaneous and coordinated interplay between AgRP and POMC neurocircuits and relayed to the NTS area by the silenced glutamatergic Npy1R neurons.
2024-02-12 | GSE248391 | GEO
Project description:Dopamine acts on neurons in the arcuate nucleus of the hypothalamus (ARC) which control homeostatic feeding responses. Here we demonstrate a differential enrichment of Drd1 expression in food intake-promoting AgRP/NPY neurons and a large proportion of Drd2-expressing anorexigenic POMC neurons. This translates into a predominant activation of AgRP/NPY neurons upon dopamine stimulation and a larger proportion of dopamine-inhibited POMC neurons. Employing intersectional targeting of Drd2-expressing POMC neurons, we reveal, that dopamine-mediated POMC neuron inhibition is Drd2-dependent and that POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators, which manifests in enhanced somatostatin responsiveness of these neurons compared to the global POMC neuron population. Retrograde pseudorabies mapping reveals predominant synaptic input onto these cells from within the ARC as well as characterized dopaminergic cell groups within the hypothalamus and subthalamic areas. Finally, selective chemogenetic activation of POMCDrd2+ neurons uncovers their ability to acutely suppress feeding and to preserve body temperature. Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids to our understanding of dopamine-dependent control of homeostatic energy regulatory neurocircuits.
2022-11-08 | GSE210311 | GEO
Project description:From the arcuate nucleus of mice, we have dissociated neurons that express Proopiomelanocortin(POMC) and captured them on the Fluidigm C1 platform. These neuronsplay important roles in the regulation of appetite and sexual behavior. Here we propose tosequence RNA from 96 single POMC-expressing neurons to understand the variance in theirtranscriptomes.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2015-04-28 | E-ERAD-357 | biostudies-arrayexpress
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
Project description:We aim at identifying genes enriched in POMC neurons versus NPY neurons that were involved in glutamatergic synapse formation
2020-02-07 | GSE144887 | GEO
Project description:We report RNA sequencing of single Agrp neurons isolated from the arcuate nucleus of the hypothalamus. Analyses of Agrp neuron transcriptomes reveals differential expression of receptors for multiple neuromodulators. Neuroanatomical mapping of known ligands of the receptors define subsets of neurons directly upstream of AgRP neurons in specific brain areas.
2023-03-27 | GSE227909 | GEO