Hypothalamic mTOR Signaling Regulates Food Intake

TLDR

mTOR is a serine‑threonine kinase that senses cellular energy status, regulates cell‑cycle progression and growth, and in the rat hypothalamus is modulated by energy availability and co‑localized with NPY and POMC neurons in the arcuate nucleus. Activation of hypothalamic mTOR by leucine or leptin suppresses food intake and body weight, and inhibition of mTOR blunts leptin’s anorectic effect, demonstrating that hypothalamic mTOR activity directly regulates energy intake.

Abstract

The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.