Preventive Cardiology-JB704, Hartford Hospital, Hartford, CT 06102-5037, USA.
J Appl Physiol (1985). 2011 Apr;110(4):1021-8. doi: 10.1152/japplphysiol.00287.2010. Epub 2011 Jan 20.
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.
肝脂肪酶 (HL) 和脂蛋白脂肪酶 (LPL) 活性 (HLA、LPLA) 可修饰脂蛋白并促进其与肝受体结合。载脂蛋白 E (APOE) 与脂肪酶物理相互作用，APOE 基因的三个常见单倍型 (ε2、ε3 和 ε4) 产生功能不同的蛋白同工型 (E2、E3 和 E4)。脂肪酶活性本身因性别和运动训练状态而异。APOE 基因型、运动训练和性别对脂肪酶活性的影响之间的相互作用尚未得到研究。我们在接受 6 个月有氧运动训练的具有三种最常见 APOE 基因型的正常血脂男性和女性中测量了肝素后血浆脂肪酶活性，这些基因型组合是 ε2/ε3 (n = 53)、ε3/ε3 (n = 62) 和 ε4/ε3 (n = 52)。这些单倍型组合分别占人群的估计 11.6%、62.3%和 21.3%。基线 HLA 在女性中比男性低 35%（P < 0.0001）。在男性中，但不是女性中，与 ε4/ε3 相比，ε2/ε3 组的 HLA 更高（P = 0.01）和 ε3/ε3（P = 0.05）。性别或 APOE 基因型均不影响基线 LPLA。训练使 HLA 降低了 5.2%（P = 0.018），APOE 无影响。运动后 LPLA 的明显增加仅在胰岛素校正后才有统计学意义，且仅在 APOE 依赖性时才有统计学意义（P < 0.05）。与 ε2/ε3 和 ε4/ε3 的组合增加 6.6%和 12%相比，ε3/ε3 中运动使 LPLA 降低了 0.8 μmol 游离脂肪酸 (FFA)·ml⁻¹·h⁻¹（-6%）（P = 0.018 与 ε3/ε3）。然而，在校正基线胰岛素后，这些差异仅具有统计学意义。我们得出结论，常见的 APOE 基因型相互作用 1）性别调节 HLA，无论训练状态如何，与 ε2/ε3 男性相比，ε3/ε3 或 ε4/ε3 男性的 HLA 更高，2）调节 LPLA 的有氧运动，无论性别如何，与 ε3/ε3 相比，ε2/ε3 和 ε3/ε4 在控制基线胰岛素后，观察到显著降低。
