LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL).

Abstract	Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, manifests as an over-accumulation of hepatic fat. We have recently shown that mice with genetic knockout of a long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) (SRAKO) are resistant to high fat diet-induced obesity with a phenotype that includes improved glucose tolerance and attenuated hepatic steatosis. The underlying mechanism was investigated in the present study. We found that hepatic levels of SRA and adipose triglyceride lipase (ATGL), a major hepatic triacylglycerol (TAG) hydrolase, were inversely regulated by fasting in mice, and the expression of liver ATGL was induced by SRAKO under normal and high fat diet (HFD) feeding. Loss of SRA in primary hepatocytes or a hepatocyte cell line upregulates, but forced expression of SRA inhibits ATGL expression and free fatty acids (FFA) β-oxidation. SRA inhibits ATGL promoter activity, primarily by inhibiting the otherwise-inductive effects of the transcription factor, forkhead box protein O1 (FoxO1). Our data reveal a novel function of SRA in promoting hepatic steatosis through repression of ATGL expression.
Authors	Gang Chen, Dongsheng Yu, Xue Nian, Junyi Liu, Ronald J Koenig, Bin Xu, Liang Sheng
Journal	Scientific reports (Sci Rep) Vol. 6 Pg. 35531 (10 19 2016) ISSN: 2045-2322 [Electronic] England
PMID	27759039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins FOXO1 protein, human Forkhead Box Protein O1 RNA, Long Noncoding RNA, Small Interfering steroid receptor RNA activator, human Lipase
Topics	Animals Carrier Proteins (genetics) Diet, High-Fat Fasting Fatty Liver (genetics, metabolism) Forkhead Box Protein O1 (genetics, metabolism) Gene Expression Regulation Hep G2 Cells Hepatocytes (physiology) Humans Lipase (genetics, metabolism) Lipid Peroxidation Liver (pathology) Mice Mice, Knockout Non-alcoholic Fatty Liver Disease (genetics, metabolism) Obesity (genetics) RNA, Long Noncoding (genetics) RNA, Small Interfering (genetics) Up-Regulation

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