Biochemical Society Transactions

672nd Meeting

Regulation of liver carnitine palmitoyltransferase I gene expression by hormones and fatty acids

J.-F. Louet, C. Le May, J.-P. Pégorier, J.-F. Decaux, J. Girard

Abstract

This brief review focuses on the transcriptional regulation of liver carnitine palmitoyltransferase I (L-CPT I) by pancreatic and thyroid hormones and by long-chain fatty acids (LCFA). Both glucagon and 3,3′,5-tri-iodothyronine (T3) enhanced the transcription of the gene encoding L-CPT I, whereas insulin had the opposite effect. Interestingly, the transcriptional effect of T3 required, in addition to the thyroid-responsive element, the co-operation of a sequence located in the first intron of L-CPT I gene. Non-esterified fatty acids rather than acyl-CoA ester or intramitochondrial metabolite were responsible for the transcriptional effect on the gene encoding LCPT I. It was shown that LCFA and peroxisome proliferators stimulated L-CPT I gene transcription by distinct mechanisms. Peroxisome proliferator stimulated L-CPT I gene transcription through a peroxisome-proliferator-responsive element (PPRE) located at -2846 bp, whereas LCFA induced L-CPT I gene transcription through a peroxisome-proliferator-activated receptor α (PPARα)-independent mechanism owing to a sequence located in the first intron of the gene.

  • long-chain fatty acids
  • pancreatic and thyroid hormones
  • PPAR
  • transcription
  • ACS, long-chain fatty acyl-CoA synthase
  • aP2, adipocyte lipid-binding protein
  • CREB, cAMP-response-elementbinding protein
  • LCFA, long-chain fatty acids
  • L-CPT I, liver carnitine palmitoyltransferase I
  • PPAR, peroxisome-proliferatoractivated receptor
  • PUFA, polyunsaturated fatty acids
  • RXR, retinoid X receptor
  • T3, 3,3′,5-tri-iodothyronine
  • TR thyroid hormone receptor
  • TRE, T3 response element