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Publication
The Signal Transducer and Activator of Transcription 1 (STAT1) Inhibits
Mitochondrial Biogenesis in Liver and Fatty Acid Oxidation in Adipocytes.
Authors Sisler JD, Morgan M, Raje V, Grande RC, Derecka M, Meier J, Cantwell M,
Szczepanek K, Korzun WJ, Lesnefsky EJ, Harris TE, Croniger CM, Larner AC
Submitted By Submitted Externally on 8/15/2017
Status Published
Journal PLoS ONE
Year 2015
Date Published
Volume : Pages 10 : e0144444
PubMed Reference 26689548
Abstract 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
PGC1a, a master regulator of mitochondrial biogenesis. STAT1 binds to the PGC1a
promoter in fed mice but not in fasted animals, suggesting that STAT1 inhibited
transcription of PGC1a. 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. ß-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.




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