title: Dietary α-tocopherol and atorvastatin reduce high-fat-induced lipid accumulation and down-regulate CD36 protein in the liver of guinea pigs.
abstract: The increased uptake and storage of lipids in the liver are important features of steatotic liver diseases. The fatty acid translocase/scavenger receptor cluster of differentiation (CD)36 facilitates the hepatic uptake of lipids. We investigated if RRR-α-tocopherol (αT) alone or in combination with atorvastatin (ATV) is capable of preventing hepatic lipid accumulation via down-regulation of CD36. To this end, Dunkin Hartley guinea pigs were fed a control diet (5% fat); or a high-fat control diet (21% fat, 0.15% cholesterol); or a high-fat control diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV+αT for 6 weeks. Hepatic triacylglycerols, hepatic protein and mRNA expression of CD36 as well as the mRNA expression of the controlling nuclear receptors LXRα, PXR and PPARγ were determined. Animals fed the high-fat control diet accumulated significantly more triacylglycerols in the liver than control animals. This was significantly reduced by ATV and numerically by αT and ATV+αT. Hepatic CD36 protein concentrations were significantly higher in the high-fat than in the control group, and both αT and ATV reduced CD36 expression to the level observed in the control group. However, no synergistic effect of the combined treatment was observed. Neither CD36 mRNA nor that of the nuclear receptors (LXRα, PXR and PPARγ) differed between groups, suggesting a posttranslational regulatory mechanism. Our results indicate that orally administered ATV and αT individually, but not synergistically, prevent diet-induced lipid accumulation in the liver of guinea pigs by down-regulation of hepatic CD36 protein.
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart, Germany.
authors.forename: Maren C
authors.initials: MC
authors.lastname: Podszun
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Grebenstein
authors.affiliation: Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Spruss
authors.affiliation: Phenex Pharmaceutical AG, D-69123 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlueter
authors.affiliation: Phenex Pharmaceutical AG, D-69123 Heidelberg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Kremoser
authors.affiliation: Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart, Germany. Electronic address: jan.frank@nutres.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D019587:Dietary Supplements; D015536:Down-Regulation / Q000187:drug effects; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D011973:Receptors, LDL / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D006538:Heptanoic Acids; D011758:Pyrroles; D011973:Receptors, LDL; D014280:Triglycerides; D000069059:Atorvastatin; D024502:alpha-Tocopherol
keywords: Atorvastatin; CD36; Fatty acid translocase; Hepatic fatty acid uptake; High-fat diet; Scavenger receptor; Steatosis; Tocopherol; Vitamin E