AgRP neurons shape the sperm small RNA payload
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE277621 | GEO | 2024/10/22
REPOSITORIES: GEO
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Project description:We investigated differentially expressed sncRNAs in human sperm as candidate markers for evaluating sperm quality during IVF. We demonstrated that differentially expressed tsRNAs, rsRNAs and miRNAs are linked to sperm quality according to embryo quality, even though these sperm samples were all considered normal by the traditional semen-parameter assessment. Therefore, the sncRNAs, especially tsRNAs and rsRNAs, may be potential clinical biomarkers for the assessment of sperm quality in IVF.
2019-02-21 | GSE110190 | GEO
Project description:Hypothalamic neurons expressing Agouti-related peptide (AgRP) are critical for initiating food intake, but druggable biochemical pathways that control this response remain elusive. Thus, genetic ablation of insulin or leptin signaling in AgRP neurons is predicted to reduce satiety but fails to do so. FoxO1 is a shared mediator of both pathways, and its inhibition is required to induce satiety. Accordingly, FoxO1 ablation in AgRP neurons of mice results in reduced food intake, leanness, improved glucose homeostasis, and increased sensitivity to insulin and leptin. Expression profiling of flow-sorted FoxO1-deficient AgRP neurons identifies G-protein-coupled receptor Gpr17 as a FoxO1 target whose expression is regulated by nutritional status. Intracerebroventricular injection of Gpr17 agonists induces food intake, whereas Gpr17 antagonist cangrelor curtails it. These effects are absent in Agrp-Foxo1 knockouts, suggesting that pharmacological modulation of this pathway has therapeutic potential to treat obesity. We used microarrays to detail the change of gene expression in AgRP neurons after knocking out FoxO1. AgRP neurons from control and KO mice were collected by FACS. Gene expression was analyzed by microarray.
2013-04-09 | E-GEOD-45858 | 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:AgRP neurons shape the sperm small RNA payload
| PRJNA1162929 | ENA
Project description:We have found that acute activation of AgRP-neurons lead to inhibition of insulin-stimulated glucose uptake into BAT. Based on this finding, we asked whether this effect was accompanied by acute changes in gene expression, which could point to the mechanism(s) underlying the impaired insulin sensitivity. In summary, our data suggest that activation of AgRP-neurons actuely reprograms gene expression in BAT towards a myogenic profile. The arcuate nucleus of 4 mice expressing channelrhodopsin 2 in AgRP-neurons through Cre-mediated recombination (ChR2-AgRP) and 4 Cre-negative controls (ChR2-fl/WT, Ctrl), were stimulated with blue laser light for one hour, total RNA from BAT was isolated and subjected to a microarray-based gene expression analysis.
2016-02-10 | E-GEOD-77766 | biostudies-arrayexpress
Project description:Objective: The central melanocortin system is essential for the regulation of food intake and body weight. Agouti-related protein (AgRP) is the sole orexigenic component of the central melanocortin system and is conserved across mammalian species. AgRP is currently known to be expressed exclusively in the mediobasal hypothalamus, and hypothalamic AgRP-expressing neurons are essential for feeding. Here we characterized a previously unknown population of AgRP cells in the mouse hindbrain. Methods: Expression of AgRP in the hindbrain was investigated using gene expression analysis, single-cell RNA sequencing, immunofluorescent analysis and multiple transgenic mice with reporter expressions. Activation of AgRP neurons was achieved by Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and by transcranial focal photo-stimulation using a step-function opsin with ultra-high light sensitivity (SOUL). Results: AgRP expressing cells were present in the area postrema (AP) and the adjacent subpostrema area (SubP) and commissural nucleus of the solitary tract (cNTS) of the mouse hindbrain (termed AgRPHind herein). AgRPHind cells consisted of locally projecting neurons as well as tanycyte-like cells. Food deprivation stimulated hindbrain Agrp expression as well as neuronal activity of subsets of AgRPHind cells. In adult mice that lacked hypothalamic AgRP neurons, chemogenetic activation of AgRP neurons resulted in hyperphagia and weight gain. In addition, transcranial focal photo-stimulation of hindbrain AgRP cells increased food intake in adult mice with or without hypothalamic AgRP neurons. Conclusions: Our study indicates that the central melanocortin system in the hindbrain possesses an orexigenic component, and that AgRPHind neurons stimulate feeding independently of hypothalamic AgRP neurons.
2024-01-23 | GSE204865 | 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:Hypothalamic neurons expressing Agouti-related peptide (AgRP) are critical for initiating food intake, but druggable biochemical pathways that control this response remain elusive. Thus, genetic ablation of insulin or leptin signaling in AgRP neurons is predicted to reduce satiety but fails to do so. FoxO1 is a shared mediator of both pathways, and its inhibition is required to induce satiety. Accordingly, FoxO1 ablation in AgRP neurons of mice results in reduced food intake, leanness, improved glucose homeostasis, and increased sensitivity to insulin and leptin. Expression profiling of flow-sorted FoxO1-deficient AgRP neurons identifies G-protein-coupled receptor Gpr17 as a FoxO1 target whose expression is regulated by nutritional status. Intracerebroventricular injection of Gpr17 agonists induces food intake, whereas Gpr17 antagonist cangrelor curtails it. These effects are absent in Agrp-Foxo1 knockouts, suggesting that pharmacological modulation of this pathway has therapeutic potential to treat obesity. We used microarrays to detail the change of gene expression in AgRP neurons after knocking out FoxO1.
2013-04-09 | GSE45858 | GEO
Project description:AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated male mouse AgRP neuron-specific transcriptomic and chromatin accessibility profiles during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 28 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons, while live-cell imaging in vitro indicate that leptin can activate neuronal IRF3 in a cell autonomous manner. Finally, we employ CUT&RUN to uncover direct transcriptional targets of IRF3 in AgRP neurons in vivo. Thus, our findings identify AgRP neuron-expressed IRF3 as a key transcriptional effector of the hunger-suppressing effects of leptin.
2024-04-12 | GSE240484 | GEO
Project description:Emerging small noncoding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in diverse biological processes, such as neurological diseases. Traditional sncRNA-seq protocols often miss these sncRNAs due to their modifications. We have recently developed PANDORA-seq, a method enabling more comprehensive detection of modified sncRNAs by overcoming the RNA modifications. Using PANDORA-seq, we have revealed an updated sncRNA profile enriched by tsRNAs/rsRNAs in the mouse cortex and found a particularly significant downregulation of mitochondrial tsRNAs and rsRNAs in an Alzheimer's disease (AD) mouse model, compared to genomic tsRNAs and rsRNAs. Moreover, our integrated analysis of cortex gene expression and sncRNA profiles reveals that those downregulated mitochondrial sncRNAs are negatively correlated with enhanced lysosomal activity, suggesting a crucial interplay between mitochondrial RNA dynamics and lysosomal function in AD. Given the versatile tsRNA/tsRNA molecular actions in cellular regulation, our data provides insights for future mechanistic study of AD with potential therapeutic strategies.
2024-12-17 | GSE277483 | GEO