Effect of diet-induced weight loss on angiopoietin-like protein 4 and adipose tissue lipid metabolism in overweight and obese humans

Angiopoietin-like protein 4 (ANGPTL4) plays a role in lipid partitioning by inhibiting lipoprotein lipase (LPL)-dependent plasma clearance of triacylglycerol in adipose tissue. We investigated the effects of diet-induced weight loss on plasma ANGPTL4 concentrations in relation to in vivo adipose tissue LPL activity and lipolysis and adipose tissue ANGPTL4 release in overweight/obese participants. Sixteen individuals (BMI: 28–35 kg/m2; 10 women) were randomized to a dietary intervention composed of either a low-calorie diet (1250 kcal/day) for 12 weeks (n = 9) or a very low-calorie diet (500 kcal/day) for 5 weeks, followed by a 4-week weight stable period. Before and after the intervention, we measured arteriovenous concentration differences in combination with adipose tissue blood flow before and after intake of a high-fat mixed meal with [U-13C]-palmitate to assess in vivo adipose tissue LPL activity and lipolysis. The intervention significantly reduced body weight (−8.6 ± 0.6 kg, P < 0.001). Plasma ANGPTL4 concentrations were unaffected. Significant postprandial adipose tissue ANGPTL4 release into the circulation was observed (P < 0.01). No association was observed between plasma ANGPTL4 and in vivo LPL activity. After intervention, fasting and postprandial plasma ANGPTL4 concentrations were positively associated with adipose tissue nonesterified FA (NEFA) and glycerol release, reflecting in vivo adipose tissue lipolysis (fasting NEFA: P = 0.039 and postprandial NEFA: P = 0.003). In conclusion, plasma ANGPTL4 is unaffected by weight loss and is secreted from human adipose tissue after a high-fat meal in overweight/obese participants. Plasma ANGPTL4 concentrations were not related to in vivo adipose tissue LPL activity, but were positively associated with in vivo adipose tissue lipolysis after weight loss.