Hypothalamic mTOR Signaling Regulates Food Intake

  title={Hypothalamic mTOR Signaling Regulates Food Intake},
  author={Daniela Cota and Karine Proulx and Kathi Smith and Sara C. Kozma and George Thomas and Stephen C. Woods and Randy J. Seeley},
  pages={927 - 930}
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… 

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

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 are summarized and highlighted.

The Role of Hypothalamic Mammalian Target of Rapamycin Complex 1 Signaling in Diet-Induced Obesity

Findings point strongly to the possibility that reduced hypothalamic mTORC1 signaling contributes to the development of hyperphagia, weight gain, and leptin resistance during diet-induced obesity.

The role of hypothalamic mTORC1 signaling in insulin regulation of food intake, body weight, and sympathetic nerve activity in male mice.

The results demonstrate the importance of mTORC1 pathway in the hypothalamus in mediating the action of insulin to regulate energy homeostasis and sympathetic nerve traffic and highlight the key role of PI3K as a link between insulin receptor and m TORC1 signaling inThe hypothalamus.

Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status.

The robust activation of mTORC1-dependent ARC pS6 in response to fasting and leptin deficiency in leptin receptor-expressing Agouti-related protein neurons is revealed, suggesting the potential stimulation of m TORC1 by the neuronal activity.

Regulation of food intake through hypothalamic signaling networks involving mTOR.

The role of hypothalamic intracellular fuel sensors in the overall control of energy balance is provided and the potential contribution of these fuel-sensing mechanisms to the metabolic dysregulation associated with obesity is discussed.

Fatty Acid Synthase Inhibitors Modulate Energy Balance via Mammalian Target of Rapamycin Complex 1 Signaling in the Central Nervous System

Findings collectively indicate an important interaction between the FAS and mTORC1 pathways in the central nervous system for regulating energy balance, possibly via modulation of neuronal glucose utilization.

The mammalian target of rapamycin pathway and its role in molecular nutrition regulation.

The mTOR signaling pathway and its interaction with food intake, insulin resistance, lifespan and adipogenic regulation during the molecular nutrition regulation is reviewed.



AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus

Hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance, and inhibition of hypothalamic AM PK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects.

Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance.

Activation of the mTOR pathway is increased in liver and muscle of high fat-fed obese rats and in vitro studies with rapamycin suggest that mTOR/S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver or muscle of this dietary model of obesity.

Dysregulation of the TSC-mTOR pathway in human disease

Emerging evidence for a functional relationship between the mTOR signaling pathway and several genetic diseases is discussed, and evidence supporting a model in which dysregulation of mTOR may be a common molecular basis for hamartoma syndromes and for other cellular hypertrophic disorders is presented.

Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia.

The hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus is supported and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling.

Regulation of mammalian translation factors by nutrients.

  • C. Proud
  • Biology
    European journal of biochemistry
  • 2002
Data indicate the operation of additional, and so far unknown, regulatory mechanisms that control eIF2B activity, which controls the recruitment of the initiator methionyl-tRNA to the ribosome and is activated by insulin in the absence of glucose or amino acids.

Hypothalamic sensing of fatty acids

There is growing evidence supporting the idea that fatty acid metabolism within discrete hypothalamic regions can function as a sensor for nutrient availability that can integrate multiple nutritional and hormonal signals.

CNS sensing and regulation of peripheral glucose levels.

Mammalian TOR: A Homeostatic ATP Sensor

It is demonstrated that the mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and that mTOR itself is an ATP sensor.