Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21
Copyright policy )Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21
Significance The mammalian target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, growth factors, and cellular energy. Aberrant mTORC1 signaling is implicated in human diseases such as diabetes, obesity, and cancer. Our results reveal that ectopic mTORC1 activation in the liver controls the stress hormone fibroblast growth factor 21 (FGF21) in a peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent manner via glutamine depletion, which in turn affects whole-body behavior and metabolism. mTORC1 signaling correlates with FGF21 expression in human liver tumors, suggesting that our findings in mice may have physiological relevance in glutamine-addicted human cancers. Thus, treatment with the anticancer drug rapamycin may have beneficial effects by blocking tumor growth and by preventing deregulation of whole-body physiology due to FGF21 expression.
- ETH Zurich Switzerland
- University of Basel Switzerland
- École Polytechnique Fédérale de Lausanne EPFL Switzerland
- University Hospital of Basel Switzerland
- Institute for Molecular Systems Biology Switzerland
Male, Mice, Knockout, Mice, Inbred BALB C, Carcinoma, Hepatocellular, Mice, 129 Strain, Glutamine, Liver Neoplasms, Mechanistic Target of Rapamycin Complex 1, Motor Activity, Lipid Metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Body Temperature, Fibroblast Growth Factors, Mice, Inbred C57BL, Mice, Liver, Gene Knockdown Techniques, Multiprotein Complexes, Animals, Humans
Male, Mice, Knockout, Mice, Inbred BALB C, Carcinoma, Hepatocellular, Mice, 129 Strain, Glutamine, Liver Neoplasms, Mechanistic Target of Rapamycin Complex 1, Motor Activity, Lipid Metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Body Temperature, Fibroblast Growth Factors, Mice, Inbred C57BL, Mice, Liver, Gene Knockdown Techniques, Multiprotein Complexes, Animals, Humans
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