Adipose-specific disruption of signal transducer and activator of transcription 3 increases body weight and adiposity.
To determine the role of STAT3 in adipose tissue, we used Cre-loxP DNA recombination to create mice with an adipocyte-specific disruption of the STAT3 gene (ASKO mice). aP2-Cre-driven disappearance of STAT3 expression occurred on d 6 of adipogenesis, a time point when preadipocytes have already undergone conversion to adipocytes. Thus, this knockout model examined the role of STAT3 in mature but not differentiating adipocytes. Beginning at 9 wk of age, ASKO mice weighed more than their littermate controls and had increased adipose tissue mass, associated with adipocyte hypertrophy, but not adipocyte hyperplasia, hyperphagia, or reduced energy expenditure. Leptin-induced, but not isoproterenol-induced, lipolysis was impaired in ASKO adipocytes, which may partially explain the increased cell size. Despite reduced adiponectin and increased liver triacylglycerol, ASKO mice displayed normal glucose tolerance. Overall, these findings demonstrate that adipocyte STAT3 regulates body weight homeostasis in part through direct effects of leptin on adipocytes.
Cernkovich
Erin R
ER
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Deng
Jianbei
J
Bond
Michael C
MC
Combs
Terry P
TP
Harp
Joyce B
JB
D017667:Adipocytes / Q000502:physiology*; D050154:Adiposity; D000818:Animals; D001835:Body Weight; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D020738:Leptin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction; D014280:Triglycerides / Q000096:biosynthesis
D020738:Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014280:Triglycerides