SRA gene knockout protects against diet-induced obesity and improves glucose tolerance [Metabolism]

March 27th, 2014 by Liu, S., Sheng, L., Miao, H., Saunders, T., MacDougald, O., Koenig, R., Xu, B.

We have recently shown that the non-coding RNA, steroid receptor RNA activator (SRA), functions as a transcriptional coactivator of PPARγ and promotes adipocyte differentiation in vitro. To assess SRA function in vivo, we have generated a whole mouse Sra1 gene knockout (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 TNFα 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.