高甘油三酯血症源于 PLIN1 相关性脂肪营养不良症中富含甘油三酯的脂蛋白分解障碍

IF 7.4 1区 医学 Q1 HEMATOLOGY Arteriosclerosis, Thrombosis, and Vascular Biology Pub Date : 2024-08-01 Epub Date: 2024-06-20 DOI:10.1161/ATVBAHA.124.320774
Bruno Vergès, Marie-Christine Vantyghem, Yves Reznik, Laurence Duvillard, Alexia Rouland, Emilie Capel, Corinne Vigouroux
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引用次数: 0

摘要

背景:编码PLIN1(perilipin-1)的PLIN1的致病变体是常染色体显性形式的家族性部分脂肪营养不良(FPL)的病因,与严重的胰岛素抵抗、肝脏脂肪变性和重要的高甘油三酯血症有关。本研究旨在破译与 PLIN1 相关的 FPL 引起高甘油三酯血症的机制:我们对 6 名受影响的患者与 13 名健康对照组和 8 名 2 型糖尿病患者进行了体内脂蛋白动力学研究。测量了血糖和血脂参数,包括血浆 LPL(脂蛋白脂肪酶)质量。对5名PLIN1突变FPL患者和3名对照组患者腹部皮下脂肪组织中的LPL mRNA和蛋白质表达进行了评估:结果:PLIN1 基因突变的 FPL 患者出现脂肪量减少、胰岛素抵抗和糖尿病(糖化血红蛋白 A1c,6.68±0.70%;2 型糖尿病患者为 7.48±1.63%;平均值±SD;P=0.27)。他们的血浆甘油三酯(5.96±3.08 mmol/L)高于对照组(0.76±0.27 mmol/L;PP=0.006)。与对照组相比,PLIN1 相关 FPL 患者的 VLDL(极低密度脂蛋白)-apoB100 向 IDL(中密度脂蛋白)/LDL(低密度脂蛋白)的间接分解率显著降低;1.79±1.38 对 5.34±2.45 池/天;P=0.003)和 IDL-apoB100 对 LDL 的间接分解率(2.14±1.44 对 7.51±4.07 池/天;P=0.005)。PLIN1 相关 FPL 患者与对照组的 VLDL-apoB100 生成量没有差异。与2型糖尿病患者相比,PLIN1相关FPL患者的VLDL-apoB100(P=0.031)和IDL-apoB100(P=0.031)的分解代谢也显著减少。PLIN1 相关 FPL 患者的血浆 LPL 质量明显低于对照组(21.03±10.08 对 55.76±13.10 ng/mL;PC 结论:我们的研究表明,与PLIN1相关的FPL引起的高甘油三酯血症是富含甘油三酯的脂蛋白(VLDL和IDL)分解明显减少的结果。这可能是由于LPL的可用性明显降低,这与脂肪组织质量下降有关。
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Hypertriglyceridemia Results From an Impaired Catabolism of Triglyceride-Rich Lipoproteins in PLIN1-Related Lipodystrophy.

Background: Pathogenic variants in PLIN1-encoding PLIN1 (perilipin-1) are responsible for an autosomal dominant form of familial partial lipodystrophy (FPL) associated with severe insulin resistance, hepatic steatosis, and important hypertriglyceridemia. This study aims to decipher the mechanisms of hypertriglyceridemia associated with PLIN1-related FPL.

Methods: We performed an in vivo lipoprotein kinetic study in 6 affected patients compared with 13 healthy controls and 8 patients with type 2 diabetes. Glucose and lipid parameters, including plasma LPL (lipoprotein lipase) mass, were measured. LPL mRNA and protein expression were evaluated in abdominal subcutaneous adipose tissue from patients with 5 PLIN1-mutated FPL and 3 controls.

Results: Patients with PLIN1-mutated FPL presented with decreased fat mass, insulin resistance, and diabetes (glycated hemoglobin A1c, 6.68±0.70% versus 7.48±1.63% in patients with type 2 diabetes; mean±SD; P=0.27). Their plasma triglycerides were higher (5.96±3.08 mmol/L) than in controls (0.76±0.27 mmol/L; P<0.0001) and patients with type 2 diabetes (2.94±1.46 mmol/L, P=0.006). Compared with controls, patients with PLIN1-related FPL had a significant reduction of the indirect fractional catabolic rate of VLDL (very-low-density lipoprotein)-apoB100 toward IDL (intermediate-density lipoprotein)/LDL (low-density lipoprotein; 1.79±1.38 versus 5.34±2.45 pool/d; P=0.003) and the indirect fractional catabolic rate of IDL-apoB100 toward LDL (2.14±1.44 versus 7.51±4.07 pool/d; P=0.005). VLDL-apoB100 production was not different between patients with PLIN1-related FPL and controls. Compared with patients with type 2 diabetes, patients with PLIN1-related FPL also showed a significant reduction of the catabolism of both VLDL-apoB100 (P=0.031) and IDL-apoB100 (P=0.031). Plasma LPL mass was significantly lower in patients with PLIN1-related FPL than in controls (21.03±10.08 versus 55.76±13.10 ng/mL; P<0.0001), although the LPL protein expression in adipose tissue was similar. VLDL-apoB100 and IDL-apoB100 indirect fractional catabolic rates were negatively correlated with plasma triglycerides and positively correlated with LPL mass.

Conclusions: We show that hypertriglyceridemia associated with PLIN1-related FPL results from a marked decrease in the catabolism of triglyceride-rich lipoproteins (VLDL and IDL). This could be due to a pronounced reduction in LPL availability, related to the decreased adipose tissue mass.

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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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