The Signal Transducer and Activator of Transcription 1 (STAT1) Inhibits Mitochondrial Biogenesis in Liver and Fatty Acid Oxidation in Adipocytes

PLoS One. 2015 Dec 21;10(12):e0144444. doi: 10.1371/journal.pone.0144444. eCollection 2015.


The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a master regulator of mitochondrial biogenesis. STAT1 binds to the PGC1α promoter in fed mice but not in fasted animals, suggesting that STAT1 inhibited transcription of PGC1α. Since STAT1-/- mice utilized more lipids we examined white adipose tissue (WAT) stores. Contrary to expectations, fasted STAT1-/- mice did not lose lipid from WAT. β-adrenergic stimulation of glycerol release from isolated STAT1-/- WAT was decreased, while activation of hormone sensitive lipase was not changed. These findings suggest that STAT1-/- adipose tissue does not release glycerol and that free fatty acids (FFA) re-esterify back to triglycerides, thus maintaining fat mass in fasted STAT1-/- mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Electron Transport Chain Complex Proteins / genetics
  • Electron Transport Chain Complex Proteins / metabolism
  • Fatty Acids / genetics
  • Fatty Acids / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondria, Liver / genetics
  • Mitochondria, Liver / metabolism*
  • Oxidation-Reduction
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Response Elements
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Triglycerides / genetics
  • Triglycerides / metabolism


  • Electron Transport Chain Complex Proteins
  • Fatty Acids
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Transcription Factors
  • Triglycerides