Involvement of the peroxisome proliferator-activated receptor α in regulating long-chain acyl-CoA thioesterases

Mary C. Hunt, Per J.G. Lindquist, Jeffrey M. Peters, Frank J. Gonzalez, Ulf Diczfalusy, Stefan E.H. Alexson

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47 Scopus citations

Abstract

Long-chain acy-CoA thioesterases catalyze the hydrolysis of acyl-CoAs to the corresponding free fatty acid and GoA. We recently cloned four members of a novel multigene family of peroxisome proliferator-induced genes encoding cytosolic (CTE-I), mitochondrial (MTE-I), and peroxisomal (PTE-Ia and PTE-Ib) acyl-CoA thioesterases (Hunt et al. 1999. J. Biol. Chem. 274: 34317-34326). As the peroxisome proliferator-activated receptor alpha (PPARα) plays a central role in regulating genes involved in lipid metabolism, we examined the involvement of this receptor in regulation of the thioesterases, particularly CTE-I and MTE-I. Northern blot analysis shows that the induction of these thioesterases by clofibrate is mediated through a strictly PPARα- dependent mechanism. All four acyl-CoA thioesterases are induced at mRNA level by fasting and using PPARα-null mice, it is evident that the increase in CTE-I due to fasting is mainly independent of the PPARα in liver and heart. The CTE-I gene responds rapidly to fasting, with induction of mRNA and protein evident after 6 h. This fasting effect is rapidly reversible, with CTE-I mRNA returning almost to control levels after 3 h refeeding, and being further repressed to 20% of control after 9 h refeeding. Although CTE-I mRNA shows a low basal expression in liver, it can be suppressed 90% by feeding a fat-free diet. These data demonstrate that the nutritional regulation of the thioesterases involves the PPARα and other signaling pathways responsible for activation and repression. Putative physiological functions for the acyl- CoA thioesterases are discussed.

Original languageEnglish (US)
Pages (from-to)814-823
Number of pages10
JournalJournal of Lipid Research
Volume41
Issue number5
StatePublished - May 2000

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

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