light research discounts the role of hepatic mTORC1 in the physiology of body -
The protein mTOR is a central controller for growth and metabolism. Dysregulation of mTOR signaling increases the risk of developing metabolic diseases such as diabetes, obesity and cancer. In the current issue of Proceedings of the National Academy of Sciences , the Basel Biozentrum of the University researchers describe how aberrant mTOR signaling in the liver not only affects the liver metabolism, but also the entire physiology of the body.
mTOR regulates cell growth and metabolism and therefore plays a key role in the development of human diseases. In the cell, the regulatory protein is located in two complexes of structurally and functionally distinct proteins called mTORC1 and mTORC2. In a recent study, the group of Prof. Michael Hall of the Biozentrum, University of Basel research has highlighted the role of mTORC1 in liver physiology of the entire body and the relevance to human liver cancers.
hepatic mTORC1 control body physiology
in mammals, the liver is a key member which controls the entire physiology of the body in response to nutrients. The Hall team investigated the role of mTORC1 nutrient sensor in the process. The researchers were able to show that the activation of mTORC1 in livers of mice not only reduces hepatic lipid metabolism, but also the locomotor activity and body temperature. After investigation of the underlying molecular mechanism, they observed that mTORC1 hyperactivation improves the level of the stress hormone FGF21 by the loss of glutamine, an amino acid. Treatment of animals with glutamine reduced the level of FGF21 and thus avoids the physiological impairments.
Cancer treatment with mTORC1 inhibitors
human cancers often exhibit aberrant mTORC1 signaling and glutamine addiction. "We were delighted to see that in the human liver tumors mTORC1 signaling correlates with the expression of FGF21" cell biologist Dr. Marion comments Cornu and first author of the study. Furthermore, mTORC1 inhibitors such as Rapamycin are presently used as immunosuppressive agents and anti-cancer drugs. Thus, new discoveries of Hall team provide evidence that the treatment of human cancers with glutamine addicted rapamycin could have beneficial effects in blocking tumor growth and preventing the deregulation of the whole body physiology .
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