Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor α activity

Jessica M. Sapiro, Mara T. Mashek, Andrew S. Greenberg, Douglas G. Mashek

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1621-1629
Number of pages9
JournalJournal of Lipid Research
Volume50
Issue number8
DOIs
StatePublished - Sep 14 2009

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Peroxisome Proliferator-Activated Receptors
Hydrolysis
Triglycerides
Liver
Proteins
Fatty Acids
Lipase
Small Interfering RNA
Perilipin-2
Metabolism
Adenoviridae
Gene expression
Rats
Hepatocytes
Assays
Genes
Ligands
Gene Expression

Keywords

  • Adipose differentiation-related protein
  • Adipose triglyceride lipase
  • Fatty acids

Cite this

Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor α activity. / Sapiro, Jessica M.; Mashek, Mara T.; Greenberg, Andrew S.; Mashek, Douglas G.

In: Journal of Lipid Research, Vol. 50, No. 8, 14.09.2009, p. 1621-1629.

Research output: Contribution to journalArticle

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