Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 19, Pages 13000-13009Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.564658
Keywords
Adipocyte; Gene Expression; Gene Knockout; Obesity; RNA
Categories
Funding
- National Institutes of Health [R01DK62876]
- Michigan Diabetes Research Center
- NIH [P30DK020572]
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Background: The non-coding RNA, steroid receptor RNA activator (SRA), promotes adipocyte differentiation in vitro. Results: SRA gene knock-out protects against obesity and improves glucose tolerance in mice fed a high fat diet. Conclusion: SRA is an important regulator of adiposity in diet-induced obesity. Significance: This is the first report that the Sra1 gene plays an important role in adipose tissue biology in vivo. We have recently shown that the non-coding RNA, steroid receptor RNA activator (SRA), functions as a transcriptional coactivator of PPAR and promotes adipocyte differentiation in vitro. To assess SRA function in vivo, we have generated a whole mouse Sra1 gene knock-out (SRA(-/-)). Here, we show that the Sra1 gene is an important regulator of adipose tissue mass and function. SRA is expressed at a higher level in adipose tissue than other organs in wild type mice. SRA(-/-) mice are resistant to high fat diet-induced obesity, with decreased fat mass and increased lean content. This lean phenotype of SRA(-/-) mice is associated with decreased expression of a subset of adipocyte marker genes and reduced plasma TNF levels. The SRA(-/-) mice are more insulin sensitive, as evidenced by reduced fasting insulin, and lower blood glucoses in response to IP glucose and insulin. In addition, the livers of SRA(-/-) mice have fewer lipid droplets after high fat diet feeding, and the expression of lipogenesis-associated genes is decreased. To our knowledge, these data are the first to indicate a functional role for SRA in adipose tissue biology and glucose homeostasis in vivo.
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