Key result
Endurance exercise training lowers ANGPTL3/8 levels ~6%, improving lipase activity and lipid profiles.
Why the study?
ANGPTL complexes 3/8 and 4/8 inhibit LPL and represent therapeutic targets for dyslipidemia, but the effects of regular exercise on them were unknown.
Does a 20-week endurance exercise training program reduce ANGPTL3/8 and ANGPTL4/8 complexes in physically inactive adults?
Does a 20-week endurance exercise training program reduce ANGPTL3/8 and ANGPTL4/8 complexes in physically inactive adults?
Exercise-induced decreases in ANGPTL3/8 and ANGPTL4/8 complexes correlate with improvements in lipase activity and cardiometabolic risk factors, revealing a potential molecular mechanism for lipid adaptations to exercise.
Endurance training-associated ANGPTL3/8 reductions may improve lipids; hypothesis-generating and requires RCTs before practice change.
Angiopoietin-like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of LPL and novel therapeutic targets for dyslipidemia. However, the effects of regular exercise on ANGPTL3/8 and ANGPTL4/8 are unknown. We characterized ANGPTL3/8 and ANGPTL4/8 and their relationship with in vivo measurements of lipase activities and cardiometabolic traits before and after a 5 month endurance exercise training intervention in 642 adults from the HERITAGE Family Study. At baseline, higher levels of both ANGPTL3/8 and ANGPTL4/8 were associated with a worse lipid, lipoprotein, and cardiometabolic profile, with only ANGPTL3/8 associated with post-heparin LPL and HL activities. ANGPTL3/8 significantly decreased with exercise training, which corresponded with increases in LPL activity and decreases in HL activity, plasma triglycerides, apoB, visceral fat, and fasting insulin (all p<5.1x10-4). Exercise-induced changes in ANGPTL4/8 were directly correlated to concomitant changes in total cholesterol, LDL-C, apoB, and HDL-triglycerides and inversely related to change in insulin sensitivity index (all p<7.0x10-4). In conclusion, exercise-induced decreases in ANGPTL3/8 and ANGPTL4/8 were related to concomitant improvements in lipase activity, lipid profile, and cardiometabolic risk factors. These findings reveal the ANGPTL3-4-8 model as a potential molecular mechanism contributing to adaptations in lipid metabolism in response to exercise training.
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Hoffmann et al. (2023) studied Healthy, physically inactive adults (n=642). Endurance exercise training vs. Baseline (pre-training) was evaluated on ANGPTL3/8 concentration (ng/ml) (MD -0.8, p=<0.05). A 20-week endurance exercise training program significantly decreased ANGPTL3/8 levels by 0.8 ng/ml compared to baseline, which correlated with improvements in lipase activity, lipid profile, and cardiometabolic risk factors.
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