Journal of Lipid Research
Volume 50, Issue 8, August 2009, Pages 1621-1629
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Research Article
Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor α activity

https://doi.org/10.1194/jlr.M800614-JLR200Get rights and content
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Recent evidence suggests that fatty acids generated from intracellular triacylglycerol (TAG) hydrolysis may have important roles in intracellular signaling. This study was conducted to determine if fatty acids liberated from TAG hydrolysis regulate peroxisome proliferator-activated receptor α (PPARα). Primary rat hepatocyte cultures were treated with adenoviruses overexpressing adipose differentiation-related protein (ADRP) or adipose triacylglycerol lipase (ATGL) or treated with short interfering RNA (siRNA) targeted against ADRP. Subsequent effects on TAG metabolism and PPARα activity and target gene expression were determined. Overexpressing ADRP attenuated TAG hydrolysis, whereas siRNA-mediated knockdown of ADRP or ATGL overexpression resulted in enhanced TAG hydrolysis. Results from PPARα reporter activity assays demonstrated that decreasing TAG hydrolysis by ADRP overexpression resulted in a 35–60% reduction in reporter activity under basal conditions or in the presence of fatty acids. As expected, PPARα target genes were also decreased in response to ADRP overexpression. However, the PPARα ligand, WY-14643, was able to restore PPARα activity following ADRP overexpression. Despite its effects on PPARα, overexpressing ADRP did not affect PPARγ activity. Enhancing TAG hydrolysis through ADRP knockdown or ATGL overexpression increased PPARα activity. These results indicate that TAG hydrolysis and the consequential release of fatty acids regulate PPARα activity.

fatty acids
adipose differentiation-related protein
adipose triglyceride lipase

Cited by (0)

    Ad-GFP

    adenovirus expressing green fluorescent protein

    ADRP

    adipose differentiation-related protein

    AMPK

    AMP-activated protein kinase

    ATGL

    adipose triacyglycerol lipase

    EPA

    eicosapentaenoic acid

    HSL

    hormone-sensitive lipase

    PPAR

    peroxisome proliferator-activated receptor

    qRT-PCR

    quantitative reverse transcription polymerase chain reaction

    siRNA

    short interfering RNA

    TAG

    triacylglycerol