title: 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.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, Jiangsu, 210029, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, Jiangsu, 210029, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Nian
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, MI 48109-5678, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Koenig
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, MI 48109-5678, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, Jiangsu, 210029, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sheng
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D059305:Diet, High-Fat; D005215:Fasting; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C548898:steroid receptor RNA activator, human; D008049:Lipase