The contribution of intraabdominal fat to gender differences in hepatic lipase activity and low/high density lipoprotein heterogeneity.
The contribution of intraabdominal fat to gender differences in hepatic lipase activity and low/high density lipoprotein heterogeneity.
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DOI：
10.1210/jcem.86.6.7586
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发表时间：
2001-06
期刊：
影响因子：
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通讯作者：
M. C. Carr;John E. Hokanson;Alberto Zambon;Samir S. Deeb;P. Hugh R. Barrett;Jonathan Q. Purnell;John D. Brunzell
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文献类型：
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作者：
M. C. Carr;John E. Hokanson;Alberto Zambon;Samir S. Deeb;P. Hugh R. Barrett;Jonathan Q. Purnell;John D. Brunzell
肝脂酶（HL）水解低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）中的甘油三酯和磷脂，HL活性升高与致动脉粥样硬化的小而致密的LDL颗粒和降低的HDL 2-C相关。HL活性升高与年龄增加、男性、大量腹内脂肪（IAF）和HL基因（LIPC）启动子多态性（C核苷酸-514）相关。我们研究了男性（n = 44）和绝经前女性（n = 63）之间HL活性差异的机制。男性的IAF明显高于男性，（分别为144.5 +/- 80.9 vs. 66.5 +/- 43.2 cm（2）; P < 0.001），HL活性较高（220.9 +/- 94.7 vs.129.9 +/- 53.5 nmol/mL.min; P < 0.001），更致密的LDL（Rf，0.277 +/- 0.032 vs. 0.300 +/- 0.024; P = 0.01），HDL 2-C（0.19 +/- 0.10 vs. 0.32 +/- 0.16 mmol/L; P < 0.001）低于女性。在调整IAF和LIPC多态性后，男性仍然比女性具有更高（但减弱）的HL活性（分别为194.5 +/- 80.4 vs.151.0 +/- 45.2; P = 0.007）和更低的HDL 2-C（0.23 +/- 0.11 vs.0.29 +/- 0.14 mmol/L; P = 0.02）。使用多元回归分析，HL活性与IAF（P < 0.001）、性别（P < 0.001）和LIPC基因型（P < 0.001）独立相关，这些因素占HL活性方差的50%。这些数据表明，IAF是HL活性性别差异的主要组成部分，但其他性别相关的差异，可能是性类固醇激素，也有助于男性与绝经前女性相比HL活性更高。男性中较高的HL活性影响LDL和HDL异质性，并可能导致心血管风险的性别差异。
Hepatic lipase (HL) hydrolyzes triglyceride and phospholipid in low and high density lipoprotein cholesterol (LDL-C and HDL-C, respectively), and elevated HL activity is associated with small, dense atherogenic LDL particles and reduced HDL2-C. Elevated HL activity is associated with increasing age, male gender, high amounts of intraabdominal fat (IAF), and the HL gene (LIPC) promoter polymorphism (C nucleotide at -514). We investigated the mechanisms underlying the difference in HL activity between men (n = 44) and premenopausal women (n = 63). Men had significantly more IAF (144.5 +/- 80.9 vs. 66.5 +/- 43.2 cm(2), respectively; P < 0.001), higher HL activity (220.9 +/- 94.7 vs.129.9 +/- 53.5 nmol/mL.min; P < 0.001), more dense LDL (Rf, 0.277 +/- 0.032 vs. 0.300 +/- 0.024; P = 0.01), and less HDL2-C (0.19 +/- 0.10 vs. 0.32 +/- 0.16 mmol/L; P < 0.001) than women. After adjusting for IAF and the LIPC polymorphism, men continued to have higher (but attenuated) HL activity (194.5 +/- 80.4 vs.151.0 +/- 45.2, respectively; P = 0.007) and lower HDL2-C (0.23 +/- 0.11 vs. 0.29 +/- 0.14 mmol/L; P = 0.02) than women. Using multiple regression, HL activity remained independently related to IAF (P < 0.001), gender (P < 0.001), and the LIPC genotype (P < 0.001), with these factors accounting for 50% of the variance in HL activity. These data suggest that IAF is a major component of the gender difference in HL activity, but other gender-related differences, perhaps sex steroid hormones, also contribute to the higher HL activity seen in men compared with premenopausal women. The higher HL activity in men affects both LDL and HDL heterogeneity and may contribute to the gender difference in cardiovascular risk.