8/1/2023 0 Comments Mch neurons mouse brain![]() ![]() Central SIRT1 is required for MCH-induced weight gain through its actions on the sympathetic nervous system. Of note, the actions of MCH are independent of agouti-related peptide (AgRP) neurons because inhibition of γ-aminobutyric acid receptor in the ARC did not prevent the orexigenic action of MCH, and the hypophagic effect of MCH silencing was maintained after chemogenetic stimulation of AgRP neurons. Remarkably, the metabolic actions of MCH are compromised in mice lacking SIRT1 specifically in POMC neurons. MCH reduces proopiomelanocortin (POMC) neuronal activity, and the SIRT1/FoxO1 pathway regulates the inhibitory effect of MCH on POMC expression. We used pharmacological and genetic approaches to show that the sirtuin 1 (SIRT1)/FoxO1 signaling pathway in the hypothalamic arcuate nucleus (ARC) mediates MCH-induced feeding, adiposity, and glucose intolerance. However, the mechanisms mediating these actions remain largely unknown. ![]() Melanin-concentrating hormone (MCH) is an important regulator of food intake, glucose metabolism, and adiposity. ![]()
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