mTORC1 signaling in energy balance and metabolic disease.
The mammalian target of rapamycin complex 1 (mTORC1) pathway regulates cellular responses to fuel availability. Recent studies have demonstrated that within the central nervous system, and in particular the hypothalamus, mTORC1 represents an essential intracellular target for the actions of hormones and nutrients on food intake and body weight regulation. By being at the crossroads of a nutrient-hormonal signaling network, mTORC1 also controls important functions in peripheral organs, such as muscle oxidative metabolism, white adipose tissue differentiation and β-cell-dependent insulin secretion. Notably, dysregulation of the mTORC1 pathway has been implicated in the development of obesity and obesity-related conditions, such as type 2 diabetes. This manuscript will therefore review recent progress made in understanding the role of the mTORC1 pathway in the regulation of energy balance and peripheral metabolism. Furthermore, we will critically discuss the potential relevance of this intracellular pathway as a therapeutic target for the treatment of metabolic disease.
Catania
C
C
INSERM U862, Avenir Group 'Physiopathology of Energy Balance and Obesity', Bordeaux, France.
Binder
E
E
Cota
D
D
D050156:Adipogenesis / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008055:Lipids / Q000096:biosynthesis; D000076222:Mechanistic Target of Rapamycin Complex 1; D008659:Metabolic Diseases / Q000628:therapy; D046912:Multiprotein Complexes; D009124:Muscle Proteins / Q000096:biosynthesis; D009765:Obesity / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D007328:Insulin; D008055:Lipids; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases