title: Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression.
abstract: BACKGROUND
  Hepatic insulin resistance is a major characteristic of type 2 diabetes mellitus. LncRNA MEG3 has been shown to correlate to hepatic glucose production; however, the underlying mechanism remains unclear. This study aims to investigate the role of MEG3 in hepatic insulin resistance.
  
  
  METHODS
  High-fat diet mice, ob/ob mice and mice primary hepatocytes were used in this study. Expression of MEG3, FoxO1, G6pc and Pepck were determined by real-time PCR. FoxO1, G6pc, Pepck, HDAC1 and HDAC3 protein levels were analyzed by western blotting. Hepatic gluconeogenesis, glycogen accumulation, triglyceride and glycogen contents were measured by corresponding assay or kit, and body weight was monitored after an overnight fast.
  
  
  RESULTS
  Gene expression of MEG3 was upregulated in high-fat diet and ob/ob mice and increased by palmitate, oleate or linoleate. MEG3 overexpression significantly increased FoxO1, G6pc, Pepck mRNA expressions and hepatic gluconeogenesis and suppressed insulin-stimulated glycogen synthesis in primary hepatocytes, whereas palmitate-induced increase of FoxO1, G6pc and Pepck protein expressions could be reversed by MEG3 interference. In addition, high fat enhanced expression of lncRNA MEG3 in hepatocytes through histone acetylation. Furthermore, MEG3 interference could reverse the up-regulation of triglyceride as well as impaired glucose tolerance and down-regulation of glucogen content in high-fat diet mice or ob/ob mice.
  
  
  CONCLUSIONS
  Upregulation of lncRNA MEG3 enhances hepatic insulin resistance via increasing foxO1expression, suggesting that MEG3 may be a potential target and therapeutic strategy for diabetes.
authors.affiliation: Department of Gerontology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China. Electronic address: flyzhu2003@126.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Yuan-Bo
authors.initials: YB
authors.lastname: Wu
authors.affiliation: Department of Gerontology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Gerontology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China. Electronic address: kangdongmei2006@sina.com.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C422882:MEG3 non-coding RNA, mouse; D062085:RNA, Long Noncoding
keywords: FoxO1; Hepatic insulin resistance; Primary hepatocytes; lncRNA MEG3