title: Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in the world. Recent studies in cultured cells and mice have shown that sirtuin, especially sirtuin 1 (SIRT1), is a key metabolic sensor for regulating metabolic homeostasis and thus has the potential to ameliorate NAFLD. For the purposes of this study, we hypothesized that the inhibition of sirtuin signaling might contribute to the development of NAFLD.
  
  
  METHODS
  Tissue was obtained from hepatectomy specimens (10 samples), and medicolegal autopsies (10 samples). Liver tissue sections were stained with H&E. Expression of sirtuin in liver tissues in NAFLD and control group was investigated by RT-PCR and Western blotting.
  
  
  RESULTS
  RT-PCR and Western blotting demonstrated decreased expression of SIRT1, SIRT3, SIRT5, and SIRT6 in the NAFLD group in comparison with the control group. Increased expression of lipogenic genes including sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC) was noted within the NAFLD group. In contrast to the other SIRT genes, the expression of SIRT4 was upregulated.
  
  
  CONCLUSIONS
  Our study provides direct evidence of the downregulation of sirtuin signaling that suppresses lipid synthesis in the liver of NAFLD patients, which may promote NAFLD development.
authors.affiliation: Department of Lemology, the First Affiliated Hospital of Shantou University Medical College, Shantou Laboratory of Cell Senescence, Shantou University Medical College, Shantou.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Lemology, the First Affiliated Hospital of Shantou University Medical College, Shantou Laboratory of Cell Senescence, Shantou University Medical College, Shantou.
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Laboratory of Cell Senescence, Shantou University Medical College, Shantou.
authors.forename: Yu-cai
authors.initials: YC
authors.lastname: Fu
authors.affiliation: Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Xing-mu
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Department of Lemology, the First Affiliated Hospital of Shantou University Medical College, Shantou southernice@126.com.
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Zhou
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D037761:Sirtuins; D000103:Acetyl-CoA Carboxylase
keywords: NAFLD; SIRT1; fatty liver; hepatic lipid metabolism; lipogenic genes; sirtuin