Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary
Background & Aims: Obesity promotes the development of nonalcoholic fatty liver diseases (NAFLDs), yet not all obese patients develop NAFLD. The underlying causes for this discrepancy remain elusive. LPGAT1 is an acyltransferase that catalyzes the remodeling of phosphatidylglycerol (PG), a mitoc...
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doaj-25d90bf9b03f46af968fce1e57b9a6822020-11-25T02:20:56ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2019-01-0174763781Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummaryXiaoyang Zhang0Jun Zhang1Haoran Sun2Xueling Liu3Yue Zheng4Dan Xu5Jianing Wang6Dandan Jia7Xianlin Han8Feng Liu9Jia Nie10Yuguang Shi11Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaSam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TexasDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaSam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TexasSam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TexasSam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TexasSam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TexasSam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TexasDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China; Sam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Correspondence Address correspondence to: Yuguang Shi, PhD, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Longmian Street 101, Nanjing, China.Background & Aims: Obesity promotes the development of nonalcoholic fatty liver diseases (NAFLDs), yet not all obese patients develop NAFLD. The underlying causes for this discrepancy remain elusive. LPGAT1 is an acyltransferase that catalyzes the remodeling of phosphatidylglycerol (PG), a mitochondrial phospholipid implicated in various metabolic diseases. Here, we investigated the role of LPGAT1 in regulating the onset of diet-induced obesity and its related hepatosteatosis because polymorphisms of the LPGAT1 gene promoter were strongly associated with susceptibility to obesity in Pima Indians. Methods: Mice with whole-body knockout of LPGAT1 were generated to investigate the role of PG remodeling in NAFLD. Results: LPGAT1 deficiency protected mice from diet-induced obesity, but led to hepatopathy, insulin resistance, and NAFLD as a consequence of oxidative stress, mitochondrial DNA depletion, and mitochondrial dysfunction. Conclusions: This study identified an unexpected role of PG remodeling in obesity, linking mitochondrial dysfunction to NAFLD. Keywords: LPGAT1, Cardiolipin, MEGDEL Syndrome, NAFLD, Mitochondrial Dysfunctionhttp://www.sciencedirect.com/science/article/pii/S2352345X19300116 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoyang Zhang Jun Zhang Haoran Sun Xueling Liu Yue Zheng Dan Xu Jianing Wang Dandan Jia Xianlin Han Feng Liu Jia Nie Yuguang Shi |
spellingShingle |
Xiaoyang Zhang Jun Zhang Haoran Sun Xueling Liu Yue Zheng Dan Xu Jianing Wang Dandan Jia Xianlin Han Feng Liu Jia Nie Yuguang Shi Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary Cellular and Molecular Gastroenterology and Hepatology |
author_facet |
Xiaoyang Zhang Jun Zhang Haoran Sun Xueling Liu Yue Zheng Dan Xu Jianing Wang Dandan Jia Xianlin Han Feng Liu Jia Nie Yuguang Shi |
author_sort |
Xiaoyang Zhang |
title |
Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary |
title_short |
Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary |
title_full |
Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary |
title_fullStr |
Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary |
title_full_unstemmed |
Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to HepatosteatosisSummary |
title_sort |
defective phosphatidylglycerol remodeling causes hepatopathy, linking mitochondrial dysfunction to hepatosteatosissummary |
publisher |
Elsevier |
series |
Cellular and Molecular Gastroenterology and Hepatology |
issn |
2352-345X |
publishDate |
2019-01-01 |
description |
Background & Aims: Obesity promotes the development of nonalcoholic fatty liver diseases (NAFLDs), yet not all obese patients develop NAFLD. The underlying causes for this discrepancy remain elusive. LPGAT1 is an acyltransferase that catalyzes the remodeling of phosphatidylglycerol (PG), a mitochondrial phospholipid implicated in various metabolic diseases. Here, we investigated the role of LPGAT1 in regulating the onset of diet-induced obesity and its related hepatosteatosis because polymorphisms of the LPGAT1 gene promoter were strongly associated with susceptibility to obesity in Pima Indians. Methods: Mice with whole-body knockout of LPGAT1 were generated to investigate the role of PG remodeling in NAFLD. Results: LPGAT1 deficiency protected mice from diet-induced obesity, but led to hepatopathy, insulin resistance, and NAFLD as a consequence of oxidative stress, mitochondrial DNA depletion, and mitochondrial dysfunction. Conclusions: This study identified an unexpected role of PG remodeling in obesity, linking mitochondrial dysfunction to NAFLD. Keywords: LPGAT1, Cardiolipin, MEGDEL Syndrome, NAFLD, Mitochondrial Dysfunction |
url |
http://www.sciencedirect.com/science/article/pii/S2352345X19300116 |
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