Background and objective: CD36 is implicated in fatty-acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD). We explored this association further by investigating correlations between sCD36 levels, intrahepatic lipid content and markers of obesity in NAFLD patients and controls.
Methods: In total, 111 NAFLD patients and 33 normal/overweight controls were included. Intrahepatic lipid content was measured by magnetic resonance spectroscopy; and subgroups of participants had a dual-energy X-ray absorptiometry (n=99), magnetic resonance imaging (n=94, subcutaneous and visceral adipose tissue) and liver biopsy (n=28 NAFLD patients) performed. Plasma sCD36 was assessed by enzyme-linked immunosorbent assay.
Results: NAFLD patients had elevated sCD36 levels compared with controls (0.68 (0.12-2.27) versus 0.43 (0.10-1.18), P<0.01). sCD36 correlated with intrahepatic lipid (rs=0.30), alanine transaminase (ALT) (r=0.31), homeostasis model assessment index-insulin resistance (r=0.24), high-density lipoprotein (r=-0.32) and triglyceride (r=0.44, all P<0.01). Intrahepatic lipid and plasma triglyceride were independent predictors of sCD36 levels in a multiple regression analysis. Further, sCD36 and body mass index were weakly correlated (r=0.17, P=0.04); yet, we found no correlations between sCD36 and other measures of fat distribution except an inverse relation to visceral adipose tissue (rs=-0.21, P<0.05). We observed a trend for correlation between sCD36 and hepatic CD36 mRNA expression (r=0.37, P=0.07).
Conclusions: sCD36 levels increased with the level of intrahepatic lipid, insulin resistance and dyslipidemia. The weak association with markers of obesity and the association with hepatic CD36 mRNA expression suggest that excess sCD36 in NAFLD patients is derived from the hepatocytes, which may support that CD36 is involved in NAFLD development. An unhealthy and unbalanced CD36 expression in adipose and hepatic tissue may shift the fatty-acid load to the liver.