Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2

Diego A. Miranda, Timothy R. Koves, David A. Gross, Alexandra Chadt, Hadi Al-Hasani, Gary W. Cline, Gary J. Schwartz, Deborah M. Muoio, David L. Silver

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Triacylglyceride stored in cytosolic lipid droplets (LDs) constitutes a major energy reservoir in most eukaryotes. The regulated turnover of triacylglyceride in LDs provides fatty acids for mitochondrial β-oxidation and ATP generation in physiological states of high demand for energy. The mechanisms for the formation of LDs in conditions of energy excess are not entirely understood. Fat storage-inducing transmembrane protein 2 (FIT2/FITM2) is the anciently conserved member of the fat storage-inducing transmembrane family of proteins implicated to be important in the formation of LDs, but its role in energy metabolism has not been tested. Here, we report that expression of FIT2 in mouse skeletal muscle had profound effects on muscle energy metabolism. Mice with skeletal muscle-specific overexpression of FIT2 (CKF2) had significantly increased intramyocellular triacylglyceride and complete protection from high fat diet-induced weight gain due to increased energy expenditure. Mass spectrometry- based metabolite profiling suggested that CKF2 skeletal muscle had increased oxidation of branched chain amino acids but decreased oxidation of fatty acids. Glucose was primarily utilized in CKF2 muscle for synthesis of the glycerol backbone of triacylglyceride and not for glycogen production. CKF2 muscle was ATP-deficient and had activated AMP kinase. Together, these studies indicate that FIT2 expression in skeletal muscle plays an unexpected function in regulating muscle energy metabolism and indicates an important role for lipid droplet formation in this process.

Original languageEnglish (US)
Pages (from-to)42188-42199
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number49
DOIs
StatePublished - Dec 9 2011

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Energy Metabolism
Muscle
Skeletal Muscle
Fats
Muscles
Lipids
Proteins
Fatty Acids
Adenosine Triphosphate
Branched Chain Amino Acids
AMP-Activated Protein Kinases
Oxidation
High Fat Diet
Eukaryota
Glycogen
Glycerol
Weight Gain
Mass Spectrometry
Lipid Droplets
Nutrition

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Miranda, D. A., Koves, T. R., Gross, D. A., Chadt, A., Al-Hasani, H., Cline, G. W., ... Silver, D. L. (2011). Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2. Journal of Biological Chemistry, 286(49), 42188-42199. https://doi.org/10.1074/jbc.M111.297127

Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2. / Miranda, Diego A.; Koves, Timothy R.; Gross, David A.; Chadt, Alexandra; Al-Hasani, Hadi; Cline, Gary W.; Schwartz, Gary J.; Muoio, Deborah M.; Silver, David L.

In: Journal of Biological Chemistry, Vol. 286, No. 49, 09.12.2011, p. 42188-42199.

Research output: Contribution to journalArticle

Miranda, DA, Koves, TR, Gross, DA, Chadt, A, Al-Hasani, H, Cline, GW, Schwartz, GJ, Muoio, DM & Silver, DL 2011, 'Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2', Journal of Biological Chemistry, vol. 286, no. 49, pp. 42188-42199. https://doi.org/10.1074/jbc.M111.297127
Miranda, Diego A. ; Koves, Timothy R. ; Gross, David A. ; Chadt, Alexandra ; Al-Hasani, Hadi ; Cline, Gary W. ; Schwartz, Gary J. ; Muoio, Deborah M. ; Silver, David L. / Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 49. pp. 42188-42199.
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