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Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to Hepatosteatosis.
Cell Mol Gastroenterol Hepatol ; 7(4): 763-781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30831319
ABSTRACT
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.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: Cell Mol Gastroenterol Hepatol Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China