Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643

Ségolène Arnauld, Marco Fidaleo, Marie Claude Clémencet, Grégory Chevillard, Anne Athias, Joseph Gresti, Ronald J. Wanders, Norbert Latruffe, Valérie Nicolas-Francès, Stéphane Mandard

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The peroxisomal 3-ketoacyl-CoA thiolase B (Thb) gene was previously identified as a direct target gene of PPARalpha, a nuclear hormone receptor activated by hypolipidemic fibrate drugs. To better understand the role of ThB in hepatic lipid metabolism in mice, Sv129 wild-type and Thb null mice were fed or not the selective PPARalpha agonist Wy14,643 (Wy). Here, it is shown that in contrast to some other mouse models deficient for peroxisomal enzymes, the hepatic PPARalpha signaling cascade in Thb null mice was normal under regular conditions. It is of interest that the hypotriglyceridemic action of Wy was reduced in Thb null mice underlining the conclusion that neither thiolase A nor SCPx/SCP2 thiolase can fully substitute for ThB in vivo. Moreover, a significant increased in the expression of lipogenic genes such as Stearoyl CoA Desaturase-1 (SCD1) was observed in Thb null mice fed Wy. Elevation of Scd1 mRNA and protein levels led to higher SCD1 activity, through a molecular mechanism that is probably SREBP1 independent. In agreement with higher SCD1, enrichment of liver mono-unsaturated fatty acids of the n-7 and n-9 series was found in Thb null mice fed Wy. Overall, we show that the reduced peroxisomal β-oxidation of fat observed in Thb null mice fed Wy is associated with enhanced hepatic lipogenesis, through the combined elevation of microsomal SCD1 protein and activity. Ultimately, not only the amount but also the quality of the hepatic fatty acid pool is modulated upon the deletion of Thb.

Original languageEnglish
Pages (from-to)1376-1386
Number of pages11
JournalBiochimie
Volume91
Issue number11-12
DOIs
Publication statusPublished - Nov 2009

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Acetyl-CoA C-Acyltransferase
PPAR alpha
Stearoyl-CoA Desaturase
Fatty Acids
Modulation
Liver
Genes
Monounsaturated fatty acids
Fibric Acids
Cytoplasmic and Nuclear Receptors
Hypolipidemic Agents
Proteins
Lipogenesis
Fats
pirinixic acid
Mouse Acaa1b protein
Oxidation
Unsaturated Fatty Acids
Messenger RNA
Lipid Metabolism

Keywords

  • Mono-unsaturated fatty acids n-7 and n-9
  • Peroxisomal 3-ketoacyl-CoA thiolase B
  • PPARα
  • Stearoyl-CoA desaturase-1
  • Wy14,643

ASJC Scopus subject areas

  • Biochemistry

Cite this

Arnauld, S., Fidaleo, M., Clémencet, M. C., Chevillard, G., Athias, A., Gresti, J., ... Mandard, S. (2009). Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643. Biochimie, 91(11-12), 1376-1386. https://doi.org/10.1016/j.biochi.2009.09.004

Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643. / Arnauld, Ségolène; Fidaleo, Marco; Clémencet, Marie Claude; Chevillard, Grégory; Athias, Anne; Gresti, Joseph; Wanders, Ronald J.; Latruffe, Norbert; Nicolas-Francès, Valérie; Mandard, Stéphane.

In: Biochimie, Vol. 91, No. 11-12, 11.2009, p. 1376-1386.

Research output: Contribution to journalArticle

Arnauld, S, Fidaleo, M, Clémencet, MC, Chevillard, G, Athias, A, Gresti, J, Wanders, RJ, Latruffe, N, Nicolas-Francès, V & Mandard, S 2009, 'Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643', Biochimie, vol. 91, no. 11-12, pp. 1376-1386. https://doi.org/10.1016/j.biochi.2009.09.004
Arnauld, Ségolène ; Fidaleo, Marco ; Clémencet, Marie Claude ; Chevillard, Grégory ; Athias, Anne ; Gresti, Joseph ; Wanders, Ronald J. ; Latruffe, Norbert ; Nicolas-Francès, Valérie ; Mandard, Stéphane. / Modulation of the hepatic fatty acid pool in peroxisomal 3-ketoacyl-CoA thiolase B-null mice exposed to the selective PPARalpha agonist Wy14,643. In: Biochimie. 2009 ; Vol. 91, No. 11-12. pp. 1376-1386.
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