title: SRA gene knockout protects against diet-induced obesity and improves glucose tolerance.
abstract: 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 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 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.
authors.affiliation: From the Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes.
authors.forename: Shannon
authors.initials: S
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Sheng
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Miao
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Saunders
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Koenig
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D006706:Homeostasis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha; C405423:steroid receptor RNA activator
keywords: Adipocyte; Gene Expression; Gene Knockout; Obesity; RNA