Interactive effects ofAPOEhaplotype, sex, and exercise on postheparin plasma lipase activities

Abstract

Hepatic lipase (HL) and lipoprotein lipase (LPL) activities (HLA, LPLA) modify lipoproteins and facilitate their binding to hepatic receptors. Apolipoprotein E (APOE) physically interacts with the lipases, and the three common haplotypes of the APOE gene (ε2, ε3, and ε4) yield protein isoforms (E2, E3, and E4, respectively) that are functionally different. Lipase activities themselves differ by sex and exercise training status. The interaction of APOE genotype, exercise training, and sex effects on lipase activities has not been studied. We measured postheparin plasma lipase activities in normolipidemic men and women with the three most common APOE genotypes, which are the haplotype combinations ε2/ε3 (n = 53 ), ε3/ε3 (n = 62), and ε4/ε3 (n = 52), enrolled in 6 mo of aerobic exercise training. These haplotype combinations comprise an estimated 11.6, 62.3, and 21.3% of the population, respectively. Baseline HLA was 35% lower in women than in men (P < 0.0001). In men but not women, HLA was higher in ε2/ε3 group compared with ε4/ε3 (P = 0.01) and ε3/ε3 (P = 0.05). Neither sex nor APOE genotype affected baseline LPLA. Training decreased HLA by 5.2% (P = 0.018) with no APOE effect. The apparent increase in LPLA following exercise was significant and APOE dependent only when corrected for baseline insulin (P < 0.05). Exercise decreased LPLA by 0.8 μmol free fatty acid (FFA)·ml⁻¹·h⁻¹ (-6%) in ε3/ε3 compared with the combined increases of 6.6% in ε2/ε3 and 12% in ε4/ε3 (P = 0.018 vs. ε3/ε3). However, these differences were statistically significant only after correcting for baseline insulin. We conclude that common APOE genotypes interact with 1) sex to modulate HLA regardless of training status, with ε2/ε3 men demonstrating higher HLA than ε3/ε3 or ε4/ε3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with ε3/ε3 subjects showing a significant decrease compared with an increase in ε2/ε3 and ε3/ε4 after controlling for baseline insulin.

Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene‐targeted replacement mice

“…In contrast to body weight and fat mass, the limited literature data on APOE genotype and energy metabolism is more consistent. There is evidence that individuals carrying ε3/ε4 have greater increase in maximum oxygen consumption (VO 2max ) in response to training than homozygous ε3 carriers though baseline VO 2max were not significantly different . VO 2max is a marker of exercise performance and thus related to mitochondrial performance and energy metabolism, e.g., in skeletal muscle.…”

Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

“…Studies have found LPL activity to be increased [ 30 - 32 ] but also unchanged [ 33 , 34 ] in the early post-exercise period, increased [ 12 ] and unchanged [ 11 ] on the morning after exercise. Other studies have reported increases in LPL activity that are restricted to certain muscle fibre types [ 19 ], timepoints [ 35 ], genders [ 36 ] and apo E haplotypes [ 37 ]. In this recent genetic study [ 37 ], exercise training actually reduced post-heparin LPL activity in the most common apo E haplotype, though this did not prevent a reduction in serum TG.…”

Advances in Exercise, Fitness, and Performance Genomics in 2015

“…During the past year, one study with a large sample size examined the interaction of genetic markers identified through GWAS with physical activity and high-density lipoprotein cholesterol (HDL-C) levels (1), while two studies with small sample sizes analyzed the associations between genetic markers and exercise-related adaptations of lipid and lipoprotein metabolism (10,40).…”

“…In another study, Seip et al (40) measured postheparin plasma lipase activities in sedentary normolipidemic men and women with the three most common apolipoprotein (APOE) haplotypes, ε2/ε3 (n = 53), ε3/ε3 (n = 62), and ε4/ε3 (n = 52), enrolled in 6 months of standardized aerobic exercise training. Exercise training decreased LPL activity in the APOE 3/3 haplotype compared with increases in haplotypes 2/3 and 4/3, independent of sex, with this difference being significant only after correcting for baseline insulin (40). However, although both studies are based on standardized exercise intervention protocols, they suffer from the limitation of small sample sizes.…”