ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with obesity
ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with obesity
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DOI：
10.1002/osp4.311
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发表时间：
2019-02-01
影响因子：
2.2
通讯作者：
Baroni, M. G.
中科院分区：
文献类型：
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作者：
Bailetti, D.;Bertoccini, L.;Baroni, M. G.
目的 ANGPTL4 抑制脂肪组织中的脂蛋白脂肪酶，调节血浆甘油三酯水平。在肥胖人群中，血浆 ANGPTL4 水平与体脂量、TG 水平和低 HDL 呈正相关。 ANGPTL4 中的 E40K 功能丧失突变可阻止 LPL 抑制，从而导致普通人群中 TG 降低和 HDLc 升高。由于肥胖决定代谢改变，因此是心血管疾病的主要危险因素，因此目的是探索 ANGPTL4-E40K 突变是否可以改变与肥胖相关的代谢异常。方法 在 1206 名意大利参与者中筛查 ANGPTL4-E40K，其中 863 名（71.5%）患有肥胖症。所有非糖尿病受试者均接受 OGTT 并计算胰岛素敏感性指数。结果 携带 E40K 变异的肥胖参与者的 TG 显着降低 (p = 0.001)，HDLc 水平显着升高 (p = 0.024)。在整个人群中，E40K 携带者也证实了低 TG 和高 HDLc。在肥胖亚群中，观察到几乎所有 E40K 携带者都在 TG 的最低四分位数内 (p = 1.1 x 10(-9))。 E40K对糖代谢没有显着影响。最后，肥胖的 E40K 携带者中没有一个患有 T2D，并且加上良好的血脂状况，他们类似于代谢健康的肥胖 (MHO) 表型，相比之下，38% 的 E40E 野生型肥胖者患有糖尿病和/或血脂异常 (p = 0.0106)。结论 在肥胖参与者中，ANGPTL4-E40K 变异可预防血脂异常。肥胖E40K携带者的表型是没有代谢改变的肥胖患者的表型，类似于代谢健康肥胖的表型。
Objective ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. Methods ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. Results Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 x 10(-9)). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia (p = 0.0106). Conclusions In participants with obesity the ANGPTL4-E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.