Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA559533 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9940480.fastq.gz | Fastqsanger.gz | |||
| SRR9940490.fastq.gz | Fastqsanger.gz | |||
| SRR9940481.fastq.gz | Fastqsanger.gz | |||
| SRR9940491.fastq.gz | Fastqsanger.gz | |||
| SRR9940482.fastq.gz | Fastqsanger.gz |
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Project description:Maternal unbalanced nutritional habits during embryo development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing “diabesity” risk. Here we report that exposure to high-fat diet during gestation and lactation did not interfere with progeny’s hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for neuronal aberrant development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early-life and adulthood. Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.
2020-02-20 | GSE135639 | GEO
Project description:OBJECTIVE:Maternal unbalanced nutritional habits during embryonic development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing obesity-associated diabetes risk. However, the underlying molecular mechanisms remain largely unknown. In this study we sought to determine the translatomic signatures associated with pro-opiomelanocortin (POMC) neuron malprogramming in maternal obesogenic conditions. METHODS:We used the RiboTag mouse model to specifically profile the translatome of POMC neurons during neonatal (P0) and perinatal (P21) life and its neuroanatomical, functional, and physiological consequences. RESULTS:Maternal high-fat diet (HFD) exposure did not interfere with offspring's hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for aberrant neuronal development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early life and adulthood. CONCLUSIONS:Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.
| S-EPMC7152705 | biostudies-literature
Project description:Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes in energy state has remained unaddressed. Here, we show that sensory food perception rapidly induces mitochondrial fission in the liver via protein kinase B/AKT-dependent phosphorylation of serine 131 of the Mitochondrial fission factor (MFFS131), and this response is mediated via activation of hypothalamic Pro-opiomelanocortin (POMC)-expressing neurons. A non-phosphorylatable MFFS131G knock-in mutation abrogates AKT-induced mitochondrial fragmentation in vitro. In vivo, MFFS131G knock-in mice display altered liver mitochondrial dynamics upon food perception and refeeding and impaired insulin stimulated suppression of gluconeogenesis. Collectively, we reveal a critical role for rapid activation of a hypothalamic/liver axis to adapt mitochondrial function to anticipated changes of nutritional state in control of hepatic glucose metabolism. The repository contains two LC-MS/MS datasets aiming for the detection of phosphorylated peptides. a) POMC neuron activation and b) time course experiment of fasted, refed and caged food. We assumed that due to the short time (30 min max) that the total protein level remain unchanged.
2024-03-28 | PXD044227 | Pride
Project description:The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of 'Ghost' neurons endowed with atypical molecular and functional identity. Compared to 'classical' Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are ‘invisible’ to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers increase in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus, highlighting the ability of specialized neurons to adapt their funcitonal identity to adult-onset obesogenic stimuli
2024-04-29 | GSE261715 | 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:Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny of these critical hypothalamic neuronal populations is largely unknown. Here, we reveal novel cellular fates of the hypothalamic Pomc-expressing precursors by combining mouse genetics with a conditional viral ribosome-tagging approach to phenotype neurons. Our results show that the Pomc-expressing precursors differentiate into discrete neuronal subpopulations that mediate not only energy balance (POMC and AgRP) but also reproductive physiology (Kisspeptin). Punches containing the mediobasal hypothalamus of Pomc-Cre:RiboTag mice and Pomc-Cre mice injected with the RiboTag viral vector (AAV-DIO-RiboTag) were homogenized and incubated with anti-hemagglutin (HA) antibodies and protein A/G magnetic beads to isolate the polysome-associated mRNAS in the Pomc-derived lineage and in adult POMC neurons, respectively. To identify differentially expressed transcripts, RNA from the immunoprecipitates was extracted, amplified, labelled and hybridized to MouseRef-8 v2 expression beadchips.
2015-04-16 | E-GEOD-56917 | biostudies-arrayexpress
Project description:In this study, we aimed at uncovering the molecular mechanisms underlying POMC neuron sensory activation and the mediated behavioral and metabolic processes. Unexpectedly, we found that glycogen metabolism is rapidly engaged in POMC neurons upon sensory food perception. Genetic deletion of glycogen synthase, the sole enzyme able to make glycogen in vivo, in POMC neurons impedes food-related sensory activation while causing impairments in food awareness, short-term food intake and insulin release. These perturbations associate with whole-body metabolic defects, including overweight and insulin resistance, that are exacerbated by high-dense diets or ageing. Collectively, our study identifies glycogen metabolism as an unanticipated mechanistic driver of POMC neuron sensory activation and provides paradigm-shift evidences of the importance of neuronal glycogen for physiology.
2024-01-31 | GSE224274 | GEO
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:Classical activation of the hypothalamic-pituitary-adrenal axis (HPA) is exerted by stimulation of pituitary POMC gene transcription and ACTH release by the hypothalamic hormone CRH. In parallel, inflammatory cytokines such as IL6 and LIF also stimulate ACTH release and POMC transcription through the JAK/STAT pathway. In recent years, a particular interest in the role of the EGF pathway for POMC activation was sparked by the identification of causative mutations in the USP8 gene that have been implicated in formation of pituitary corticotrope adenomas that are the hallmark of Cushing’s disease. These mutations were associated with persistent upregulation of the EGF/EGFR pathway and its putative role in ACTH hypersecretion. In the present work, we reassessed the signalling pathways that are activated in response to ACTH in pituitary corticotrope cells using the AtT-20 cell model. We confirmed activation of the MAP kinase pathway by EGF but also show activation of the AKT/mTOR and JAK/STAT pathways. Whereas activation of all three pathways appears essential for stimulation of cell proliferation, only the JAK/STAT pathway and more specifically STAT3, enhances POMC gene transcription. This action is mapped to a single STAT binding element of the POMC promoter in contrast to activation by the other STAT-activating cytokines LIF and IL6. Further, EGF signalling is specifically enhanced by STAT3 but not STAT1 in contrast to LIF-dependent activation. All together, the data identified a unique STAT3-dependent target on the POMC promoter that mediates EGF activation of POMC gene transcription.
2025-11-03 | GSE292424 | GEO
Project description:Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny of these critical hypothalamic neuronal populations is largely unknown. Here, we reveal novel cellular fates of the hypothalamic Pomc-expressing precursors by combining mouse genetics with a conditional viral ribosome-tagging approach to phenotype neurons. Our results show that the Pomc-expressing precursors differentiate into discrete neuronal subpopulations that mediate not only energy balance (POMC and AgRP) but also reproductive physiology (Kisspeptin).
2015-04-16 | GSE56917 | GEO