The signling mTOR impairs whole body physiology

The researcheres from the Biozentrum of the University of Basel find that aberrant mTOR signaling in the liver not only affects hepatic metabolism but also whole body physiology. The result was published in Proceedings of the National Academy of Sciences.

The protein mTOR is a central controller of growth and metabolism. Deregulation of mtor inhibitors signaling increases the risk of developing metabolic diseases. In the cell, this regulatory protein is found in two structurally and functionally distinct protein complexes called mTORC1 and mTORC2. mTORC1 hyperactivation enhances the level of the stress hormone FGF21 by depletion of the amino acid glutamine. Treatment of animals with glutamine reduced the level of FGF21 and thus prevented the physiological impairments. So the activation of mTORC1 in the liver of mice reduces not only hepatic lipid metabolism but also locomotor activity and body temperature.

mTORC1 inhibitors such as rapamycin are currently used as immunosuppressive agents and anti-cancer drugs. Thus, the novel findings provide evidence that treatment of glutamine addicted human cancers with rapamycin might have beneficial effects by blocking tumor growth and by preventing deregulation of whole body physiology.

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