UCP2-dependent redox sensing in POMC neurons regulates feeding.

ABSTRACT: Paradoxically, glucose, the primary driver of satiety, activates a small population of anorexigenic pro-opiomelanocortin (POMC) neurons. Here, we show that lactate levels in the circulation and in the cerebrospinal fluid are elevated in the fed state and the addition of lactate to glucose activates the majority of POMC neurons while increasing cytosolic NADH generation, mitochondrial respiration, and extracellular pyruvate levels. Inhibition of lactate dehydrogenases diminishes mitochondrial respiration, NADH production, and POMC neuronal activity. However, inhibition of the mitochondrial pyruvate carrier has no effect. POMC-specific downregulation of Ucp2 (Ucp2^PomcKO), a molecule regulated by fatty acid metabolism and shown to play a role as transporter in the malate-aspartate

SUBMITTER: Yoon NA 

PROVIDER: S-EPMC9885759 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature