A possible link between BDNF and mTOR in control of food intake

Abstract

Food intake is intricately regulated by glucose, amino acids, hormones, neuropeptides, and trophic factors through a neural circuit in the hypothalamus. Brain-derived neurotrophic factor (BDNF), the most prominent neurotrophic factor in the brain, regulates differentiation, maturation, and synaptic plasticity throughout life. Among its many roles, BDNF exerts an anorexigenic function in the brain. However, the intracellular signaling induced by BDNF to control food intake is not fully understood. One candidate for the molecule involved in transducing the anorexigenic activity of BDNF is the mammalian target of rapamycin (mTOR). mTOR senses extracellular amino acids, glucose, growth factors, and neurotransmitters, and regulates anabolic reactions response to these signals. Activated mTOR increases protein and lipid synthesis and inhibits protein degradation. In the hypothalamus, mTOR activation is thought to reduce food intake. Here we summarize recent findings regarding BDNF- and mTOR-mediated feeding control, and propose a link between these molecules in eating behavior.

Keywords: AMPK; BDNF; body weight; food intake regulation; mTOR; mTORC1; nutrients.

FIGURE 1

Simplified schematic of upstream and downstream mTORC1 signaling.

FIGURE 2

Hypothetical roles of mTORC1 on metabolism and food intake, comparing the cellular and organismal levels. Through the activation of mTORC1, cells that receive nutrients and growth factors grow by increasing total levels of proteins and lipids. Cells (neurons) in the brain activate mTORC1 in response to nutrients and a variety of feeding-related factors. The resultant signals give the order to stop eating and maintain whole-body homeostasis.