Background

Reduced triglyceride clearance due to impaired lipoprotein lipase–mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy. Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4 levels are altered in lipodystrophy and the effects of leptin replacement on these ANGPTLs are unknown.

Objective

To examine if ANGPTL3/4 levels are elevated in patients with generalized lipodystrophy and assess the effects of leptin replacement on these ANGPTLs.

Methods

Preleptin treatment plasma levels of ANGPTLs in patients with generalized lipodystrophy (n = 22) were compared with healthy controls (n = 39) using a post hoc case-control study design. In a prospective open-label study, we studied the effects of metreleptin therapy (16–32 weeks) on plasma ANGPTL3/4 in patients with generalized lipodystrophy.

Results

Plasma ANGPTL3 (geometric mean [95% confidence interval]; 223 [182–275] vs 174 ng/mL [160–189], P = .02) but not ANGPTL4 levels (55 [37–81] vs 44 ng/mL [37–52], P = .26) were higher in patients with lipodystrophy compared with healthy controls. There was a significant decrease in total cholesterol, triglycerides, and glycosylated hemoglobin (A1C) levels following metreleptin therapy. After metreleptin, ANGPTL3 concentrations decreased significantly (223 [182–275] vs 175 ng/mL [144–214], P = .01) with no change in ANGPTL4 (55 [37–81] vs 48 ng/mL [32–73], P = .11).

Conclusions

These findings suggest that elevated plasma levels of ANGPTL3 in leptin-deficient states is attenuated with leptin therapy.

中文翻译：

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Metreleptin疗法可降低泛发性脂肪营养不良患者的血浆血管生成素样蛋白3。

背景

由于脂蛋白脂肪酶介导的脂解作用受损而导致甘油三酯清除率降低，导致脂肪营养不良的严重高甘油三酯血症。血管生成素样蛋白3（ANGPTL3）和4（ANGPTL4）通过抑制脂蛋白脂酶来破坏甘油三酸酯的清除。脂营养不良症中循环的ANGPTL3 / 4水平是否改变以及瘦素替代对这些ANGPTL的影响尚不清楚。

目的

要检查广义脂肪营养不良患者的ANGPTL3 / 4水平是否升高，并评估瘦素替代对这些ANGPTL的影响。

方法

使用事后病例对照研究设计，将广义脂代谢障碍患者（n = 22）中前瘦素治疗的血浆ANGPTLs水平与健康对照组（n = 39）进行了比较。在一项前瞻性开放标签研究中，我们研究了甲氨蝶呤治疗（16–32周）对全身性脂肪营养不良患者血浆ANGPTL3 / 4的影响。

结果

血浆ANGPTL3（几何平均值[95％置信区间]； 223 [182-275] vs 174 ng / mL [160-189]，P  = .02），但不是ANGPTL4水平（55 [37-81] vs 44 ng / mL [37-52]，P  = 0.26）脂肪营养不良的患者比健康对照者更高。甲氨蝶呤治疗后，总胆固醇，甘油三酸酯和糖基化血红蛋白（A1C）水平显着降低。甲氨蝶呤治疗后，ANGPTL3浓度显着降低（223 [182–275] vs 175 ng / mL [144–214]，P  = 0.01），而ANGPTL4无变化（55 [37–81] vs 48 ng / mL [32–32] 73]，P  = .11）。

结论

这些发现表明，在瘦素缺乏状态下，瘦素治疗降低了ANGPTL3的血浆水平。