title: Association of serum retinoic acid with hepatic steatosis and liver injury in nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Retinoic acid (RA), an active metabolite of vitamin A (retinol), has been implicated in the regulation of lipid metabolism and hepatic steatosis in animal models. However, the relation between RA and liver histology in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is unknown.
  
  
  OBJECTIVE
  This study aimed at examining the association of RA with NAFLD and NASH in Chinese subjects.
  
  
  METHODS
  Serum RA concentration was determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38 patients with NASH. The associations of RA with adiposity, serum glucose, lipid profiles, and markers of liver damage were studied. Moreover, both mRNA and protein levels of retinoic X receptor α (RXRα) in the liver were analyzed in subjects with different degrees of hepatic steatosis.
  
  
  RESULTS
  Serum RA concentrations in patients with NAFLD (1.42 ± 0.47 ng/mL) and NASH (1.14 ± 0.26 ng/mL) were significantly lower than those in control subjects (2.70 ± 0.52 ng/mL) (P < 0.01). Furthermore, serum RA concentrations were significantly different between subjects with normal glucose tolerance and those with type 2 diabetes in control [2.87 ± 0.52 (n = 28) vs. 2.32 ± 0.44 ng/mL (n = 13)], NAFLD [1.61 ± 0.37 (n = 29) vs. 1.28 ± 0.41 ng/mL (n = 16)], and NASH [1.35 ± 0.34 (n = 24) vs. 1.07 ± 0.29 ng/mL (n = 14)] groups. In human liver tissue, RXRα mRNA expression was inversely correlated with the exacerbation of hepatic steatosis. Both serum RA concentrations and RXRα mRNA levels were inversely correlated with intrahepatic triglyceride content (r = -0.700, P < 0.001, and r = -0.611, P = 0.002, respectively). Compared with grade 0 severity, the concentration of RXRα protein was lower in more severe grades in patients with NAFLD.
  
  
  CONCLUSIONS
  These results show that circulating RA concentrations were lower in subjects with NAFLD and were associated with hepatic lipid metabolism and insulin resistance. This trial was registered at clinicaltrials.gov as NCT01940263.
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China xiamin@mail.sysu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications / Q000453:epidemiology*; D012333:RNA, Messenger / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D047488:Retinoid X Receptors / Q000097:blood; D014212:Tretinoin / Q000008:administration & dosage / Q000097:blood*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D047488:Retinoid X Receptors; D014280:Triglycerides; D014212:Tretinoin
keywords: NAFLD; RXRα; hepatic steatosis; insulin resistance; retinoic acid