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Effect of dietary saturated fatty acids on HNF-4α DNA binding activity and ApoCIII mRNA in sedentary rat liver

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Abstract

Hind limb-suspended rats represent a sedentary-hyperinsulinemic model with a liver dyslipidemia mainly related to changes in sterol regulatory element-binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor-α (PPARα) expression and activity. To assess the effects of dietary fatty acids on hepatic lipid homeostasis, the hepatic expression and activity of PPARα, SREBP-1, and hepatocyte nuclear factor-4α (HNF-4α) were investigated in this animal model. In control and sedentary rats, diets enriched with saturated, monounsaturated, and polyunsaturated fatty acids (PUFA) enhanced the expression of the PPARα target genes carnitine palmitoyltransferase 1 and acyl-CoA oxidase, the highest effect being exerted by ω-3. The same diets reduced SREBP-1 mRNA and target lipogenic gene expression, as indicated by the reduction in fatty acid synthase and acetyl-CoA carboxylase mRNA content. Effects were greater in sedentary rat liver than in controls on the same diet. Only the ω-3 enriched diet decreased liver triglyceride content as well as plasma cholesterol and triglyceride levels in sedentary rats. This effect may be mainly related to the enhanced mitochondrial and peroxisomal β-oxidation genes expression. On the other hand, saturated fatty acid-enriched diet induced an increase in liver triglyceride content and enhanced plasma cholesterol and triglyceride levels, both in control and immobilized rats. This detrimental effect may be ascribed to the induced HNF-4α binding activity on ApoCIII promoter and to the enhanced ApoCIII mRNA levels both in control and in sedentary rat livers. In conclusion, we can speculate that dietary saturated fats, acting at apolipoprotein transcriptional level, may impact on the close relationship existing among high ApoCIII plasma level, dyslipidemia, and atherosclerosis.

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Abbreviations

SREBP-1:

Sterol regulatory element-binding protein 1

ACC:

Acetyl-CoA carboxylase

FAS:

Fatty acid synthase

PPARα:

Peroxisome proliferator-activated receptor-α

CPT-1:

Carnitine palmitoyltransferase 1

ACO:

Acyl-CoA oxidase

HNF-4α:

Hepatocyte nuclear factor-4α

ApoCIII:

Apolipoprotein CIII

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Acknowledgments

The authors thank Dr. Geraldine Boyd for revising the manuscript. This work was supported by a grant from the Italian Space Agency.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 3, 06122, Perugia, Italy

    Veronica Ceccarelli, Giuseppe Nocentini, Carlo Riccardi, Emira Ayroldi, Rita Roberti, Luciano Binaglia & Alba Vecchini

  2. Cellular & Molecular Cardiology Laboratory, Department of Internal Medicine, “Tor Vergata”, University of Rome, Rome, Italy

    Paolo Di Nardo

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  1. Veronica Ceccarelli
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  2. Giuseppe Nocentini
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Correspondence to Alba Vecchini.

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Ceccarelli, V., Nocentini, G., Riccardi, C. et al. Effect of dietary saturated fatty acids on HNF-4α DNA binding activity and ApoCIII mRNA in sedentary rat liver. Mol Cell Biochem 347, 29–39 (2011). https://doi.org/10.1007/s11010-010-0609-0

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