Hypothalamic mTOR Signaling Regulates Food Intake

@article{Cota2006HypothalamicMS,
  title={Hypothalamic mTOR Signaling Regulates Food Intake},
  author={D. Cota and K. Proulx and Kathi Smith and S. Kozma and G. Thomas and S. Woods and R. Seeley},
  journal={Science},
  year={2006},
  volume={312},
  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… Expand
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References

SHOWING 1-10 OF 31 REFERENCES
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
TLDR
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. Expand
AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism.
TLDR
Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes. Expand
Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance.
TLDR
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. Expand
Dysregulation of the TSC-mTOR pathway in human disease
TLDR
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. Expand
Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia.
TLDR
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. Expand
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
TLDR
It is described that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis. Expand
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
TLDR
When leptin was delivered systemically to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake, suggesting that leptin-mediated plasticity in the Ob/ob hypothalamus may underlie some of the hormone's behavioral effects. Expand
Regulation of mammalian translation factors by nutrients.
  • C. Proud
  • Biology, Medicine
  • European journal of biochemistry
  • 2002
TLDR
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. Expand
Hypothalamic sensing of fatty acids
TLDR
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. Expand
CNS sensing and regulation of peripheral glucose levels.
TLDR
Glucosensing neurons are clearly a distinct class of metabolic sensors with the capacity to respond to a variety of intero- and exteroceptive stimuli, and it is likely that they participate in physiologically relevant homeostatic mechanisms involving energy balance and the regulation of peripheral glucose levels. Expand
...
1
2
3
4
...