title: Influence of mTOR in energy and metabolic homeostasis.
abstract: The mechanistic (or mammalian) target of rapamycin couples a variety of different environmental signals, including nutrients and hormones, with the regulation of several energy-demanding cellular functions, spanning from protein and lipid synthesis to mitochondrial activity and cytoskeleton dynamics. mTOR forms two distinct protein complexes in cells, mTORC1 and mTORC2. This review focuses on recent advances made in understanding the roles played by these two complexes in the regulation of whole body metabolic homeostasis. Studies carried out in the past few years have shown that mTORC1 activity in the hypothalamus varies by cell and stimulus type, and that this complex is critically implicated in the regulation of food intake and body weight and in the central actions of both nutrients and hormones, such as leptin, ghrelin and triiodothyronine. As a regulator of cellular anabolic processes, mTORC1 activity in the periphery favors adipogenesis, lipogenesis, glucose uptake and beta-cell mass expansion. Much less is known about the function of mTORC2 in the hypothalamus, while in peripheral organs this second complex exerts roles strikingly similar to those described for mTORC1. Deregulation of mTORC1 and mTORC2 is associated with obesity, type 2 diabetes, cancer and neurodegenerative disorders. Insights on the exact relationship between mTORC1 and mTORC2 in the context of the regulation of metabolic homeostasis and on the specific molecular mechanisms engaged by these two complexes in such regulation may provide new avenues for therapy.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Haissaguerre
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Saucisse
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France. Electronic address: daniela.cota@inserm.fr.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cota
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D050356:Lipid Metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: Energy balance; Hormone; Hypothalamus; Leptin; mTORC1; mTORC2