Effects of exercise training on ANGPTL3/8 and ANGPTL4/8 and their associations with cardiometabolic traits

Angiopoietin-like protein (ANGPTL) com-plexes 3/8 and 4/8 are established inhibitors of LPLand novel therapeutic targets for dyslipidemia. How-ever, the effects of regular exercise on ANGPTL3/8and ANGPTL4/8 are unknown. We characterizedANGPTL3/8 and ANGPTL4/8 and their relationshipwith in vivo measurements of lipase activities andcardiometabolic traits before and after a 5-monthendurance exercise training intervention in 642adults from the HERITAGE (HEalth, RIsk factors,exercise Training And GEnetics) Family Study. Atbaseline, higher levels of both ANGPTL3/8 andANGPTL4/8 were associated with a worse lipid, lipo-protein, and cardiometabolic profile, with onlyANGPTL3/8 associated with postheparin LPL and HLactivities. ANGPTL3/8 significantly decreased withexercise training, which corresponded with increasesin LPL activity and decreases in HL activity, plasmatriglycerides, apoB, visceral fat, and fasting insulin (allP<5.1 10(-4)) pound. Exercise-induced changes inANGPTL4/8 were directly correlated to concomitantchanges in total cholesterol, LDL-C, apoB, and HDL-triglycerides and inversely related to change in insu-lin sensitivity index (allP<7.0 10(-4)) pound. In conclusion,exercise-induced decreases in ANGPTL3/8 andANGPTL4/8 were related to concomitant improve-ments in lipase activity, lipid profile, and car-diometabolic risk factors.These findings reveal theANGPTL3-4-8 model as a potential molecular mecha-nism contributing to adaptations in lipid metabolismin response to exercise training.