Serum Angiopoietin-like peptide 4 levels in patients with hepatic steatosis

Abstract

Objectives: Angiopoietin-like peptide 4 (ANGPTL-4) plays an important role in lipid metabolism by inhibiting the enzyme lipoprotein lipase. This effect of ANGPTL-4 results in suppression of the release of plasma triglyceride-derived fatty acids. Increase in fatty acid levels entering to the liver and abnormalities in their secretion is one of the main mechanisms in pathogenesis of hepatic steatosis. In this study, we aimed to investigate the role of ANGPTL-4 in pathogenesis of hepatic steatosis by determining its levels in patients with fatty liver disease.

Methods: Totally 51 patients (age: 37.9 ± 9.9 years, M/F) diagnosed with grade 2-3 hepatic steatosis with ultrasound and 30 healthy volunteers (age: 34.8 ± 9.5 years, M/F) were included in the study. In both groups, routine biochemical tests including fasting blood glucose, fasting insulin levels, triglyceride, total cholesterol, LDL- cholesterol, HDL-cholesterol, AST, ALT, ALP, GGT levels were measured together with the ANGPTL-4 levels. In determination of ANGPTL-4 levels, ELISA was performed.

Results: When compared with the control group, ANGPTL-4 levels were determined to be decreased in patients with hepatic steatosis (369 ± 243 vs 303 ± 286 ng/mL, p = 0.014). There was a negative weak correlation observed between ANGPTL-4 and triglyceride levels (r = -0.246, p = 0.027). Among all groups, when patients with and without insulin resistance were compared; ANGPTL-4 levels were determined to be similar. While fasting blood glucose levels were similar between 2 groups; fasting insulin and triglyceride levels were determined to be increased in hepatic steatosis group (Insulin 17.7 ± 12 vs 7.4 ± 3.3 µIU/mL, p < 0.001, triglyceride 158 ± 46.4 vs 118 ± 59.8 mg/dL p < 0.001).

Conclusions: We have determined lower serum ANGPTL-4 levels in patients with hepatic steatosis. ANGPTL-4 that is regulating LPL activity plays an important role in fatty liver disease pathogenesis via free fatty acid metabolism and peroxisome proliferator-activated receptor-delta (PPAR-δ). We believe that the results of this study would elucidate the investigations about the mechanism of fatty liver disease development and treatments targeting ANGPTL-4.

Keywords: Angiopoietin-like peptide 4; Fatty liver disease; Hepatic steatosis; Liver; Liver disease.