Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis

Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E994-E1002. doi: 10.1152/ajpendo.00121.2016. Epub 2016 May 10.

Abstract

Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes.

Keywords: energy homeostasis; hormones; hypothalamus; mTOR; nutrients.

Publication types

  • Review

MeSH terms

  • Animals
  • Body Weight / physiology
  • Eating / physiology*
  • Energy Metabolism / physiology*
  • Feedback, Physiological / physiology
  • Homeostasis / physiology*
  • Hormones / metabolism*
  • Humans
  • Hypothalamus / physiology*
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism*
  • Signal Transduction / physiology
  • Systems Integration
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Hormones
  • Multiprotein Complexes
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases