Reducing neuronal nitric oxide synthase (nNOS) expression in the ventromedial hypothalamus (VMH) increases body weight and blood glucose levels while decreasing physical activity in female mice.

Glucose-inhibited (GI) neurons of the ventromedial hypothalamus (VMH) depend on neuronal nitric oxide synthase (nNOS) and AMP-activated protein kinase (AMPK) for activation in low glucose. The Lopez laboratory has shown that the effects of estrogen on brown fat thermogenesis and white fat browning require inhibition of VMH AMPK. This effect of estrogen was mediated by downstream lateral hypothalamus (LH) orexin neurons (1,2).