Regulation of angiopoietin-like 4 and lipoprotein lipase in human adipose tissue

Dijk, Wieneke; Schutte, Sophie; Aarts, Edo O.; Janssen, Ignace M.C.; Afman, Lydia; Kersten, Sander


Background: Elevated plasma triglycerides are increasingly viewed as a causal risk factor for coronary artery disease. One protein that raises plasma triglyceride levels and that has emerged as a modulator of coronary artery disease risk is angiopoietin-like 4 (ANGPTL4). ANGPTL4 raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of circulating triglycerides on the capillary endothelium. Objective: The objective of the present study was to assess the association between ANGPTL4 and LPL in human adipose tissue, and to examine the influence of nutritional status on ANGPTL4 expression. Methods: We determined ANGPTL4 and LPL mRNA and protein levels in different adipose tissue depots in a large number of severely obese patients who underwent bariatric surgery. Furthermore, in 72 abdominally obese subjects, we measured ANGPTL4 and LPL mRNA levels in subcutaneous adipose tissue in the fasted and postprandial state. Results: ANGPTL4 mRNA levels were highest in subcutaneous adipose tissue, whereas LPL mRNA levels were highest in mesenteric adipose tissue. ANGPTL4 and LPL mRNA levels were strongly positively correlated in the omental and subcutaneous adipose tissue depots. In contrast, ANGPTL4 and LPL protein levels were negatively correlated in subcutaneous adipose tissue, suggesting a suppressive effect of ANGPTL4 on LPL protein abundance in subcutaneous adipose tissue. ANGPTL4 mRNA levels were 38% higher in the fasted compared to the postprandial state. Conclusion: Our data provide valuable insights into the relationship between ANGPTL4 and LPL in human adipose tissue, as well as the physiological function and regulation of ANGPTL4 in humans.