Effects of Klf4 deletion from Agrp expressing cells under chow or HFD conditions
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE225038 | GEO | 2024/06/03
REPOSITORIES: GEO
Similar Datasets
Project description:Effects of Klf4 deletion from Agrp expressing cells under chow or HFD conditions
| PRJNA933607 | ENA
Project description:Proteomics of liver tissue from mice fed a high fat diet (HFD) or regular chow diet. Data accompany our paper entitled “Dynamic Regulation of N6,2′-O-dimethyladenosine (m6Am) in Obesity” scheduled for publication in Nature Communications, 2021
2021-10-27 | PXD029280 | Pride
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:The molecular control of feeding after fasting is essential for maintaining energy homeostasis, and overfeeding usually leads to obesity. RNA interference has been clinically successful in managing diseases, and the identification of a feeding-regulated microRNA (miRNA), which remains a challenge, could be a strategy for combating obesity. By performing a comprehensive genome-wide microRNA screening in the arcuate nucleus of the hypothalamus (ARC) of fasted mice and ad libitum mice, we found a significant increase in miR-7a-5p levels after fasting. miR-7a-5p was highly expressed in the ARC, and inhibition of miR-7a-5p specifically in AgRP neurons reduced food intake and body weight gain. miR-7a-5p inhibited S6K1 gene expression by binding to its 3’-UTR. Furthermore, the reduction of food intake by anti-miR-7a-5p was partially reversed by the downregulated mechanistic target of rapamycin complex 1 (mTOR1)/ribosomal S6 kinase 1 (S6K1) signaling in the AgRP neurons. Importantly, intracerebroventricular administration of the miR-7a-5p inhibitor could reduce food intake and body weight. Collectively, our findings suggest miR-7a-5p as an orexigenic factor in AgRP neurons and a potential novel target for obesity treatment.
2025-01-01 | GSE254021 | GEO
Project description:Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C epsilon (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCε protects against high fat diet-induced hepatic insulin resistance. Here we employ a systems level approach to uncover additional signaling pathways involved in high fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high fat-fed, and high fat-fed with PKCε knockdown rats to distinguish the impact of lipid- and PKCε-induced protein phosphorylation.
2018-08-30 | PXD010209 | Pride
Project description:Microglia, the resident immune cells in the brain, have been shown to significantly influence neurodevelopment. However, their role in shaping the postnatal development of hypothalamic neural circuits remains underexplored. In this study, we investigated the dynamic changes of microglia in the hypothalamic arcuate nucleus (ARC) during lactation and their impact on the maturation of AgRP and POMC neurons.
2023-09-26 | GSE243697 | 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:Gene expression in livers of male wild-type (WT) and OGG1-deficient (Ogg1-/-) mice fed either a chow diet or a high-fat diet (HFD) were examined. Mice were fed the diet for 10 weeks prior to tissue collection and were 22 weeks of age at the time of tissue collection. 24 Total samples were analyzed. We generated the following pairwise comparisons using GeneSifter: WT Chow vs Ogg1-/- Chow; WT HFD vs. Ogg1-/- HFD using t-test followed by Benjamini and Hochberg correction. An adjusted p-value less than 0.05 was considered to be statistically significant.
2012-12-16 | E-GEOD-35497 | 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:This experiment was designed to investigate the effect of Fumonisin B1 exposure on liver gene expression in male mice fed a regular diet (Chow group) and in obese mice which were fed a High fat diet (HFD). The Fumonisin B1 was provided through the drinking water.
2023-09-01 | GSE208735 | GEO