Premium
Hepatic Adipose Triglyceride Lipase (ATGL) mediates hepatic triglyceride turnover, fatty acid channeling and PPAR‐alpha activity
Author(s) -
Ong Kuok Teong,
Mashek Mara,
Mashek Douglas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.694.12
Subject(s) - adipose triglyceride lipase , triglyceride , steatosis , medicine , chemistry , fatty acid , adipose tissue , endocrinology , lipoprotein lipase , gene knockdown , lipase , lipolysis , hepatocyte , lipid droplet , beta oxidation , peroxisome , biochemistry , biology , enzyme , in vitro , gene , cholesterol
Adipose triglyceride lipase (ATGL) catalyzes the first step in triglyceride (TAG) hydrolysis. Because most studies have focused on ATGL in adipose tissue, its role and function in other tissues is relatively unknown. To elucidate the metabolic functions of hepatic ATGL, we employed gain and loss‐of‐function studies in primary hepatocyte cultures and adenovirus‐mediated knockdown in vivo. ATGL overexpression in primary hepatocyte cultures exhibited resistance to fatty acid‐induced steatosis, increased catabolism of hydrolyzed fatty acids and increased PPAR‐α activity. Treament of hepatocytes with siRNA against ATGL resulted in decreased rates of TAG hydrolysis and increased TAG accumulation along with suppressed fatty acid oxidation and PPAR‐α activity. However, the large changes in TAG turnover and fatty acid oxidation did not affect media TAG suggesting that rates of VLDL synthesis were unaltered. Interestingly, ATGL shRNA‐treated mice exhibited 150% more hepatic TAG and increased liver weight. Serum TAG levels of the mice did not change in response to ATGL knockdown while the expression of PPAR‐α and its target genes decreased, thus supporting the previous data from in vitro studies. Taken together, these data show that ATGL is a major TAG lipase in the liver that acts, perhaps in part through PPAR‐α, to channel hydrolyzed fatty acids towards oxidative pathways as opposed to VLDL secretory pathways.