Feeding Neurons Integrate Metabolic and Reproductive States in Mice
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PROVIDER: PRJNA930400 | ENA |
REPOSITORIES: ENA
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Project description:Metabolic and reproductive processes interact in ways that are important for survival, particularly in mammals that gestate their young. Puberty and reproduction, as energetically taxing life stages, are often gated by metabolic availability in animals with ovaries. How the nervous system coordinates these interactions is an active area of study. We identify somatostatin (SST) neurons of the tuberal hypothalamus as a cell type in the feeding circuitry that alters feeding in a manner sensitive to metabolic and reproductive states in mice. Whereas chemogenetic activation of SST neurons increased food intake across sexes, selective ablation decreased food intake only in female mice during proestrus. Interestingly, this ablation effect was only apparent in animals with a low body mass. Fat transplantation and bioinformatics analysis of SST neuronal transcriptomes revealed white adipose as a key modulator of the effects of SST neurons on food intake. Together, these studies point to a mechanism whereby SST hypothalamic neurons modulate feeding by responding to varying levels of circulating estrogens differentially based on energy stores. This research provides insight into how neural circuits integrate reproductive and metabolic signals and illustrates how gonadal steroid modulation of neuronal circuits can be context-dependent and gated by metabolic status.
2023-07-27 | GSE224254 | GEO
Project description:Trade-offs between metabolic and reproductive processes are important for survival, particularly in mammals that gestate their young. Puberty and reproduction, as energetically taxing life stages, are often gated by metabolic availability in animals with ovaries. How the nervous system coordinates these trade-offs is an active area of study. We identify somatostatin neurons of the tuberal nucleus (TNSST) as a node of the feeding circuit that alters feeding in a manner sensitive to metabolic and reproductive states in mice. Whereas chemogenetic activation of TNSST neurons increased food intake across sexes, selective ablation decreased food intake only in female mice during proestrus. Interestingly, this ablation effect was only apparent in animals with a low body mass. Fat transplantation and bioinformatics analysis of TNSST neuronal transcriptomes revealed white adipose as a key modulator of the effects of TNSST neurons on food intake. Together, these studies point to a mechanism whereby TNSST hypothalamic neurons modulate feeding by responding to varying levels of circulating estrogens differentially based on energy stores. This research provides insight into how neural circuits integrate reproductive and metabolic signals, and illustrates how gonadal steroid modulation of neuronal circuits can be context-dependent and gated by metabolic status.
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Project description:Genetic identification of vagal sensory neurons that control feeding
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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:Paradoxically, glucose, the primary driver of satiety, activates a small population of anorexigenic POMC neurons. Here we show that lactate levels in the circulation and in the cerebrospinal fluid are elevated in fed state and addition of lactate to glucose activates the majority of POMC neurons while increasing cytosolic NADH generation, mitochondrial respiration and extracellular pyruvate levels. Inhibition of lactate dehydrogenases diminishes mitochondrial respiration, NADH production, and POMC neuronal activity. However, inhibition of the mitochondrial pyruvate carrier has no effect. POMC-specific downregulation of Ucp2 (Ucp2PomcKO), a molecule regulated by fatty acid metabolism and shown to play a role as transporter in the malate-aspartate shuttle, abolishes lactate- and glucose-sensing of POMC neurons. Ucp2PomcKO mice have impaired glucose metabolism and are prone to obesity on a high fat diet. Altogether, our data show that lactate through redox signaling and blocking mitochondrial glucose utilization activates POMC neurons to regulate feeding and glucose metabolism.
2022-11-28 | ST002361 | MetabolomicsWorkbench
Project description:microRNA-33 controls feeding behavior by activating hypothalamic AgRP neurons
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Project description:Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.
2019-11-14 | GSE138651 | GEO
Project description:Adult reproductive behaviors in Drosophila melanogaster males and females are vastly different. Yet, neurons that express sex-specifically spliced fruitless transcripts (fru P1) underlie these behaviors in both sexes. How the same set of neurons can drive such different behaviors is an important and unresolved question in developmental genetics. A particular challenge is that fru P1-expressing neurons are only 2-5% of the adult nervous system, making studies of adult head tissue, or even the whole brain, unlikely to yield informative inferences. Translating Ribosome Affinity Purification (TRAP) identifies the actively translated pool of mRNAs from fru P1-expressing neurons and allowed us to conduct a sensitive, cell-specific assay of gene expression. The male and female fru P1-expressing neurons have a shared set of 1,642 genes with enriched TRAP transcripts that form a distinct repertoire, relative to TRAP analyses of all neurons in the adult head. Further, there are a striking number of genes (3,147) that have sex-biased TRAP enrichment in fru P1-expressing neurons. Yet, most of these genes (3,107) have only male-biased TRAP enrichment. This suggests an underlying mechanism to generate dimorphism in behavior, with the transcript repertoire that specifies female behaviors present in both sexes and a large additional set of genes with expression in the male dramatically altering the pattern. Thus, these additional genes invoke the male-specific behaviors by establishing cell fate in the same context of gene expression observed in females. These results suggest a possible global mechanism for how distinct behaviors can arise in different environments, from a shared set of neurons. Libraries were prepared from five independent biological replicates, from TRAP adult heads samples from males and females, and the mRNA input from adult heads from males and females. For each experimental condition, approximately 1,000 flies that were 8 to 24 hours post-eclosion were used.
2015-09-01 | E-GEOD-67743 | biostudies-arrayexpress
Project description:Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are central regulators of fertility and integrate endogenous hormonal status with environmental cues to ensure reproductive success. Here, we found that extra-hypothalamic GnRH neurons in the olfactory bulb of adult mice and humans (GnRHOB) can mediate social recognition. We show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the hypothalamic median eminence. We demonstrate that male GnRHOB neurons express vomeronasal and olfactory receptors, are activated by female odors in vivo, and mediate gonadotropin release in response to female urine. We find that male preference for female odors is enhanced upon chemogenetic activation of GnRHOB neurons and is impaired after genetic inhibition or ablation of these cells and relies on GnRH signaling in the posterodorsal medial amygdala. Taken together, these results establish GnRHOB neurons as a central regulatory hub regulating fertility, sex recognition, and mating in males.
2024-06-17 | GSE268138 | GEO