Sirt1 rescues the obesity induced by insulin-resistant constitutively-nuclear FoxO1 in POMC neurons of male mice

摘要: Objective The hypothalamus is the brain center that controls energy balance. Anorexigenic proopiomelanocortin (POMC) neurons and orexigenic AgRP in arcuate nucleus of plays critical roles balance regulation. FoxO1 a transcription factor regulated by insulin signaling deacetylated Sirt1, nicotinamide adenine dinucleotide- (NAD+-) dependent deacetylase. Overexpression insulin-resistant constitutively-nuclear (CN-FoxO1) POMC leads to obesity, whereas Sirt1 overexpression leanness. Whether could rescue obesity caused CN-FoxO1 was tested here. Methods POMC neuron-specific CN-FoxO1/Sirt1 double-KI (DKI) mice were analyzed. Results The obese phenotype KI rescued male DKI mice. Reduced O2 consumption, increased adiposity, fewer observed without affecting food intake locomotor activity. decreased acetylation protein levels its nuclear localization mouse embryonic fibroblasts hypothalamic N41 cells. Conclusions Sirt1 rescues induced decreasing through deacetylation. ameliorates genetic model central resistance.