{"title":"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","authors":"Bruno Vergès, Marie-Christine Vantyghem, Yves Reznik, Laurence Duvillard, Alexia Rouland, Emilie Capel, Corinne Vigouroux","doi":"10.1161/ATVBAHA.124.320774","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in <i>PLIN1</i>-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 <i>PLIN1</i>-related FPL.</p><p><strong>Methods: </strong>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. <i>LPL</i> mRNA and protein expression were evaluated in abdominal subcutaneous adipose tissue from patients with 5 <i>PLIN1</i>-mutated FPL and 3 controls.</p><p><strong>Results: </strong>Patients with <i>PLIN1</i>-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; <i>P</i>=0.27). Their plasma triglycerides were higher (5.96±3.08 mmol/L) than in controls (0.76±0.27 mmol/L; <i>P</i><0.0001) and patients with type 2 diabetes (2.94±1.46 mmol/L, <i>P</i>=0.006). Compared with controls, patients with <i>PLIN1</i>-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; <i>P</i>=0.003) and the indirect fractional catabolic rate of IDL-apoB100 toward LDL (2.14±1.44 versus 7.51±4.07 pool/d; <i>P</i>=0.005). VLDL-apoB100 production was not different between patients with <i>PLIN1</i>-related FPL and controls. Compared with patients with type 2 diabetes, patients with <i>PLIN1</i>-related FPL also showed a significant reduction of the catabolism of both VLDL-apoB100 (<i>P</i>=0.031) and IDL-apoB100 (<i>P</i>=0.031). Plasma LPL mass was significantly lower in patients with <i>PLIN1</i>-related FPL than in controls (21.03±10.08 versus 55.76±13.10 ng/mL; <i>P</i><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.</p><p><strong>Conclusions: </strong>We show that hypertriglyceridemia associated with <i>PLIN1</i>-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.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1873-1883"},"PeriodicalIF":7.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hypertriglyceridemia Results From an Impaired Catabolism of Triglyceride-Rich Lipoproteins in <i>PLIN1</i>-Related Lipodystrophy.\",\"authors\":\"Bruno Vergès, Marie-Christine Vantyghem, Yves Reznik, Laurence Duvillard, Alexia Rouland, Emilie Capel, Corinne Vigouroux\",\"doi\":\"10.1161/ATVBAHA.124.320774\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pathogenic variants in <i>PLIN1</i>-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 <i>PLIN1</i>-related FPL.</p><p><strong>Methods: </strong>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. <i>LPL</i> mRNA and protein expression were evaluated in abdominal subcutaneous adipose tissue from patients with 5 <i>PLIN1</i>-mutated FPL and 3 controls.</p><p><strong>Results: </strong>Patients with <i>PLIN1</i>-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; <i>P</i>=0.27). Their plasma triglycerides were higher (5.96±3.08 mmol/L) than in controls (0.76±0.27 mmol/L; <i>P</i><0.0001) and patients with type 2 diabetes (2.94±1.46 mmol/L, <i>P</i>=0.006). Compared with controls, patients with <i>PLIN1</i>-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; <i>P</i>=0.003) and the indirect fractional catabolic rate of IDL-apoB100 toward LDL (2.14±1.44 versus 7.51±4.07 pool/d; <i>P</i>=0.005). VLDL-apoB100 production was not different between patients with <i>PLIN1</i>-related FPL and controls. Compared with patients with type 2 diabetes, patients with <i>PLIN1</i>-related FPL also showed a significant reduction of the catabolism of both VLDL-apoB100 (<i>P</i>=0.031) and IDL-apoB100 (<i>P</i>=0.031). Plasma LPL mass was significantly lower in patients with <i>PLIN1</i>-related FPL than in controls (21.03±10.08 versus 55.76±13.10 ng/mL; <i>P</i><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.</p><p><strong>Conclusions: </strong>We show that hypertriglyceridemia associated with <i>PLIN1</i>-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.</p>\",\"PeriodicalId\":8401,\"journal\":{\"name\":\"Arteriosclerosis, Thrombosis, and Vascular Biology\",\"volume\":\" \",\"pages\":\"1873-1883\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arteriosclerosis, Thrombosis, and Vascular Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/ATVBAHA.124.320774\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arteriosclerosis, Thrombosis, and Vascular Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/ATVBAHA.124.320774","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.
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.