Matches in SemOpenAlex for { <https://semopenalex.org/work/W2913016435> ?p ?o ?g. }
- W2913016435 abstract "Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss." @default.
- W2913016435 created "2019-02-21" @default.
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- W2913016435 date "2019-04-12" @default.
- W2913016435 modified "2023-10-16" @default.
- W2913016435 title "Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis" @default.
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