Association of serum retinoic acid with hepatic steatosis and liver injury in nonalcoholic fatty liver disease

作者：Liu, Yan; Chen, Hongen; Wang, Jingjing; Zhou, Wenjing; Sun, Ruifang; Xia, Min^*

来源：American Journal of Clinical Nutrition, 2015, 102(1): 130-137.

DOI：10.3945/ajcn.114.105155

• retinoic acid
• insulin resistance
• hepatic steatosis
• NAFLD
• RXR alpha

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.
Design: 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 retinoie X receptor alpha (RXR alpha) 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)1, NAFLD [1.61 /- 0.37 (n = 29) vs. 1.28 /- 0.41 ng/mL (n = 16)1, and NASH [1.35 /- 0.34 (n = 24) vs. 1.07 /- 0.29 ng/mL (n = 14)] groups. In human liver tissue, RXR alpha mRNA expression was inversely correlated with the exacerbation of hepatic steatosis. Both serum RA concentrations and RXR alpha 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 RXR alpha protein was lower in more severe grades in patients with NAFLD.
Conclusion: These results show that circulating RA concentrations were lower in subjects with NAFLD and were associated with hepatic lipid metabolism and insulin resistance.

• 出版日期2015-7
• 单位中山大学