Hypothalamic mTOR signaling regulates food intake.
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.
Cota
Daniela
D
Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA.
Proulx
Karine
K
Smith
Kathi A Blake
KA
Kozma
Sara C
SC
Thomas
George
G
Woods
Stephen C
SC
Seeley
Randy J
RJ
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D004435:Eating; D002149:Energy Intake; D004734:Energy Metabolism; D005215:Fasting; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism*; D007276:Injections, Intraventricular; D020738:Leptin / Q000494:pharmacology; D007930:Leucine / Q000008:administration & dosage* / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D038601:Ribosomal Protein S6 / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014633:Valine / Q000008:administration & dosage / Q000494:pharmacology; D015431:Weight Loss
D020738:Leptin; D009478:Neuropeptide Y; D038601:Ribosomal Protein S6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D011494:Protein Kinases; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D014633:Valine; D020123:Sirolimus