Prostaglandin E₂ activates melanin-concentrating hormone neurons to drive diet-induced obesity.

ABSTRACT: Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How hypothalamic inflammation can induce opposite energy balance outcomes remains unclear. We found that prostaglandin E₂ (PGE₂), a key hypothalamic inflammatory mediator of sickness, also mediates diet-induced obesity (DIO) by activating appetite-promoting melanin-concentrating hormone (MCH) neurons in the hypothalamus in rats and mice. The effect of PGE₂ on MCH neurons is excitatory at low concentrations while inhibitory at high concentrations, indicating that these neurons can bidirectionally respond to varying levels of inflammation. During prolonged HFD, endogenous PGE₂ depolarizes MCH neur

SUBMITTER: Fang LZ 

PROVIDER: S-EPMC10401019 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature