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Updated: Apr 26, 2026

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
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Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

Marion Cornu1, Wolfgang Oppliger1, Verena Albert1

  • 1Biozentrum, University of Basel, CH-4056 Basel, Switzerland;

Proceedings of the National Academy of Sciences of the United States of America
|August 2, 2014
PubMed

Insights

Liver mTORC1 signaling controls whole-body physiology via PGC-1α and FGF21. This pathway

Area of Science:

  • Metabolic regulation
  • Molecular biology
  • Physiology

Background:

  • The liver is a central metabolic organ.
  • Mammalian target of rapamycin (mTOR) regulates growth and metabolism.
  • Tuberous sclerosis complex 1 (TSC1) negatively regulates mTOR.

Purpose of the Study:

  • Investigate the role of liver-specific mTOR complex 1 (mTORC1) in whole-body physiology.
  • Determine the molecular mechanisms linking hepatic mTORC1 to metabolic and behavioral phenotypes.

Main Methods:

  • Generated liver-specific Tsc1 knockout (L-Tsc1 KO) mice.
  • Administered rapamycin to assess pathway sensitivity.
  • Performed glutamine injections and PGC-1α/FGF21 knockdown experiments.

Main Results:

  • L-Tsc1 KO mice showed reduced activity, body temperature, and liver triglycerides.
  • mTORC1 activation depleted hepatic and plasma glutamine.
  • This led to PGC-1α-dependent FGF21 expression, causing metabolic and behavioral defects.

Conclusions:

  • Hepatic mTORC1 signaling regulates whole-body physiology through PGC-1α and FGF21.
  • mTORC1 signaling correlates with FGF21 in human liver tumors.
  • mTOR inhibitors may benefit glutamine-addicted cancers.
Keywords:
TSCbehaviorhepatocellular carcinomametabolic stress

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