title: Mouse KLF11 regulates hepatic lipid metabolism.
abstract: OBJECTIVE
  Missense mutations in human Krüppel-like factor 11 (KLF11) lead to the development of diabetes, as a result of impaired insulin synthesis in the pancreas. However, the role of KLF11 in peripheral tissues is largely unknown. The aim of this study is to evaluate the role of KLF11 in the regulation of hepatic lipid homeostasis using different mouse models.
  
  
  METHODS
  Adenoviruses expressing KLF11 (Ad-KLF11) or KLF11-specific shRNA (Ad-shKLF11) were injected into db/db diabetic, high-fat diet-induced obese (DIO), or normal C57BL/6J mice. Histological analysis of the fatty liver phenotype and biochemical analysis of hepatic and serum TG levels in these mice were performed. The molecular mechanism by which KLF11 regulates lipid metabolism in primary hepatocytes and mouse livers was explored.
  
  
  RESULTS
  The expression of the transcription factor KLF11 gene is dysregulated in the livers of db/db and DIO mice. Adenovirus-mediated overexpression of KLF11 in the livers of db/db and DIO mice activates the PPARα signaling pathway, subsequently markedly improving the fatty liver phenotype. Conversely, knockdown of KLF11, by adenovirus (Ad-shKLF11) in livers of wild type C57BL/6J and db/m mice, increases hepatic triglyceride (TG) levels, owing to decreased fatty acid oxidation. Finally, the treatment of diabetic mice with Ad-shPPARα abolishes KLF11 stimulatory effects on the expression of genes involved in fatty acid oxidation and inhibitory effects on hepatic TG content. In contrast, PPARα rescue restores the increased hepatic TG levels in Ad-shKLF11-infected db/m mice to normal levels.
  
  
  CONCLUSIONS
  KLF11 is an important regulator of hepatic lipid metabolism.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.forename: Ning
authors.initials: N
authors.lastname: Gong
authors.forename: Anfang
authors.initials: A
authors.lastname: Cui
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Lian
authors.initials: L
authors.lastname: Shen
authors.forename: Shutian
authors.initials: S
authors.lastname: Zhang
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009752:Nutritional Status; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C506460:KLF11 protein, mouse; D047493:PPAR alpha; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; D014280:Triglycerides