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Fatty acids derived from triacylglycerol hydrolysis are a significant source of ligands for peroxisome proliferator‐activated receptor‐α (PPAR‐α) in rat primary hepatocytes
Author(s) -
Sapiro Jessica M.,
Mashek Mara T.,
Mashek Douglas G.
Publication year - 2008
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.22.1_supplement.807.19
Subject(s) - lipogenesis , peroxisome proliferator activated receptor , peroxisome , chemistry , eicosapentaenoic acid , biochemistry , polyunsaturated fatty acid , fatty acid synthase , transcription factor , oleic acid , fatty acid , receptor , intracellular , lipid metabolism , gene
Fatty acids (FAs), especially polyunsaturated fatty acids, have gained a lot of attention for their important roles in regulating transcription factors involved in hepatic energy metabolism. Intracellular FAs are derived from multiple sources including exogenous, de novo lipogenesis, and triacylglycerol (TAG) hydrolysis. However, little is known regarding how FAs from different sources affect activity of transcription factors such as PPAR‐α. Thus, the aim of this study was to determine if FAs generated from TAG hydrolysis influence PPAR‐α activity in rat primary hepatocytes. To manipulate TAG hydrolysis, we overexpressed adipose differentiated‐related protein (ADRP), which resulted in a 50% decrease in TAG turnover. Results from PPAR‐α reporter activity assays demonstrated that 250 μM eicosapentaenoic acid (EPA) alone or in combination with 250 μM oleic acid robustly increased PPAR‐α activity while overexpression of ADRP resulted in an inhibition of TAG hydrolysis and a decline in PPAR‐α activity. These results indicate that FAs generated from TAG hydrolysis are a significant source of ligands for PPAR‐α activation.