Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■编码PLIN1的PLIN1（perilipin-1）中的致病变体是与严重胰岛素抵抗相关的家族性部分脂肪营养不良（FPL）的常染色体显性形式，肝脂肪变性,和重要的高甘油三酯血症。本研究旨在破译与PLIN1相关FPL相关的高甘油三酯血症的机制。
■我们在6名受影响的患者中进行了体内脂蛋白动力学研究，与13名健康对照和8名2型糖尿病患者进行了比较。葡萄糖和脂质参数，包括血浆LPL（脂蛋白脂肪酶）质量，被测量。在5例PLIN1突变的FPL患者和3例对照的腹部皮下脂肪组织中评估LPLmRNA和蛋白表达。
■PLIN1突变FPL患者表现为脂肪量减少，胰岛素抵抗，和糖尿病（糖化血红蛋白A1c，2型糖尿病患者为6.68±0.70％与7.48±1.63％；平均值±SD；P=0.27）。他们的血浆甘油三酯（5.96±3.08mmol/L）高于对照组（0.76±0.27mmol/L;P<0.0001）和2型糖尿病患者（2.94±1.46mmol/L，P=0.006)。与对照组相比，PLIN1相关FPL患者VLDL(极低密度脂蛋白)-apoB100向IDL(中密度脂蛋白)/LDL(低密度脂蛋白;1.79±1.38vs.5.34±2.45pool/d;P=0.003)的间接分解代谢率和IDL-apoB100向LDL的间接分解代谢率(2.14±1.44vs.与PLIN1相关的FPL患者和对照组之间VLDL-apoB100的产生没有差异。与2型糖尿病患者相比，PLIN1相关FPL患者VLDL-apoB100(P=0.031)和IDL-apoB100(P=0.031)的分解代谢也显著降低.与PLIN1相关的FPL患者的血浆LPL质量显着低于对照组（21.03±10.08对55.76±13.10ng/mL；P<0.0001），尽管脂肪组织中LPL蛋白表达相似。VLDL-apoB100和IDL-apoB100间接分数分解代谢率与血浆甘油三酯呈负相关，与LPL质量呈正相关。
■我们表明与PLIN1相关的FPL相关的高甘油三酯血症是由富含甘油三酯的脂蛋白（VLDL和IDL）的分解代谢显着降低引起的。这可能是由于LPL可用性的显著降低，与脂肪组织质量减少有关。
■我们在6名受影响的患者中进行了体内脂蛋白动力学研究，与13名健康对照和8名2型糖尿病患者进行了比较。葡萄糖和脂质参数，包括血浆LPL（脂蛋白脂肪酶）质量，被测量。在5例PLIN1突变的FPL患者和3例对照的腹部皮下脂肪组织中评估LPLmRNA和蛋白表达。
■PLIN1突变FPL患者表现为脂肪量减少，胰岛素抵抗，和糖尿病（糖化血红蛋白A1c，2型糖尿病患者为6.68±0.70％与7.48±1.63％；平均值±SD；P=0.27）。他们的血浆甘油三酯（5.96±3.08mmol/L）高于对照组（0.76±0.27mmol/L;P<0.0001）和2型糖尿病患者（2.94±1.46mmol/L，P=0.006)。与对照组相比，PLIN1相关FPL患者VLDL(极低密度脂蛋白)-apoB100向IDL(中密度脂蛋白)/LDL(低密度脂蛋白;1.79±1.38vs.5.34±2.45pool/d;P=0.003)的间接分解代谢率和IDL-apoB100向LDL的间接分解代谢率(2.14±1.44vs.与PLIN1相关的FPL患者和对照组之间VLDL-apoB100的产生没有差异。与2型糖尿病患者相比，PLIN1相关FPL患者VLDL-apoB100(P=0.031)和IDL-apoB100(P=0.031)的分解代谢也显著降低.与PLIN1相关的FPL患者的血浆LPL质量显着低于对照组（21.03±10.08对55.76±13.10ng/mL；P<0.0001），尽管脂肪组织中LPL蛋白表达相似。VLDL-apoB100和IDL-apoB100间接分数分解代谢率与血浆甘油三酯呈负相关，与LPL质量呈正相关。
■我们表明与PLIN1相关的FPL相关的高甘油三酯血症是由富含甘油三酯的脂蛋白（VLDL和IDL）的分解代谢显着降低引起的。这可能是由于LPL可用性的显著降低，与脂肪组织质量减少有关。
