Hypothalamic mTOR Signaling Regulates Food Intake
Abstract
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.
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Leptin has been reported to activate AMPK and mTOR signaling pathways.
“Leptin has also been reported to activate nutrient-sensing enzymes including AMP-activated protein kinase (AMPK) (115) and mammalian target of rapamycin (mTOR) signaling pathways (41)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [41]
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LRb signals act within a distributed network of leptin‐responsive neurones to mediate leptin action
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Remodeling of lipid metabolism by dietary restriction of essential amino acids
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Molecular Targets for Obesity Therapy in the Brain
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Metabolic Regulation of Kisspeptin
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Hepatic autophagy contributes to the metabolic response to dietary protein restriction
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- Authors
- Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J.
- Affiliations
- University of Cincinnati (US)
- Corresponding author
- Seeley, Randy J.
- Venue
- Science
- Published
- 2006-05-12
- Volume
- 312
- Issue
- 5775
- Pages
- 927-930
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2067152194
- Cited by
- 1,278
- References
- 27
- Citations by year
- 2026: 26 · 2025: 33 · 2024: 43 · 2023: 46 · 2022: 43 · 2021: 50 · 2020: 50 · 2019: 61 · 2018: 60 · 2017: 62 · 2016: 68 · 2015: 72 · 2014: 83 · 2013: 84 · 2012: 108
- FWCI
- 28.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK17844, DK54080, R01DK054080, R01DK054890, DK-54890)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTOR signaling, hypothalamus, dietary intake, energy balance, arcuate nucleus, neuropeptide Y, proopiomelanocortin, leptin, leucine, nutrient sensing, anorectic effect, body weight regulation
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Energy Intake, Eating, Energy Metabolism, Fasting, Hypothalamus, Injections, Intraventricular, Leucine, Neurons, Neuropeptide Y, Phosphorylation, Protein Kinases, Valine, Signal Transduction, Weight Loss, Ribosomal Protein S6 Kinases, Sirolimus, Rats, Long-Evans, Leptin, Ribosomal Protein S6, STAT3 Transcription Factor, Rats, TOR Serine-Threonine Kinases
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