Interactive effects of APOE haplotype, sex, and exercise on postheparin plasma lipase activities

Seip RL, Zoeller RF, Angelopoulos TJ, Salonia J, Bilbie C, Moyna NM, Miles MP, Visich PS, Pescatello LS, Gordon PM, Tsongalis GJ, Bausserman L, Thompson PD. Interactive effects of APOE haplotype, sex, and exercise on postheparin plasma lipase activities. J Appl Physiol 110: 1021-1028, 2011. First published February 3, 2011; doi:10.1152/japplphysiol.00287.2010.-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 (epsilon 2, epsilon 3, and epsilon 4) 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 epsilon 2/epsilon 3 (n = 53), epsilon 3/epsilon 3 (n = 62), and epsilon 4/epsilon 3 (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 \u3c 0.0001). In men but not women, HLA was higher in epsilon 2/epsilon 3 group compared with epsilon 4/epsilon 3 (P = 0.01) and epsilon 3/epsilon 3 (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 \u3c 0.05). Exercise decreased LPLA by 0.8 mu mol free fatty acid (FFA).ml(-1).h(-1) (-6%) in epsilon 3/epsilon 3 compared with the combined increases of 6.6% in epsilon 2/epsilon 3 and 12% in epsilon 4/epsilon 3 (P = 0.018 vs. epsilon 3/epsilon 3). 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 epsilon 2/epsilon 3 men demonstrating higher HLA than epsilon 3/epsilon 3 or epsilon 4/epsilon 3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with epsilon 3/epsilon 3 subjects showing a significant decrease compared with an increase in epsilon 2/epsilon 3 and epsilon 3/epsilon 4 after controlling for baseline insulin