title: Hepatic VLDL secretion of genetically obese Zucker rats is inhibited by a high-fat diet.
abstract: Hepatocytes from obese and lean Zucker rats adapted to a control (C) or a high-fat (HF) diet were prepared for the study of fatty acid (FA) uptake, partition between oxidation and esterification, and very low density lipoprotein (VLDL) production. A first 2-h kinetic study showed higher oleate uptake on a C diet by obese rat cells and an almost exclusive esterification to triacylglycerol (TG), VLDL secretion being 2.5-fold higher in obese rat cells and enhanced 1.4-fold in both genotypes in the presence of 0.7 mM oleate vs. 0.1 mM or no oleate. Fat feeding 1) decreased oleate uptake, esterification, incorporation into VLDL-TG, and mass VLDL-TG secretion and 2) abolished the VLDL-TG increase by 0.7 mM oleate. Similar but more pronounced effects were obtained in fat-fed lean animals. A second kinetic study using very short incubation times up to 1 h confirmed that fat feeding decreased oleate uptake and esterification, greatly stimulating its oxidation and production of acetoacetate (obese) or acetoacetate and beta-hydroxybutyrate (lean). Synthesis of lactate and pyruvate greatly decreased under HF feeding, remaining higher in obese rat cells. The drastic inhibition of labeled and total hepatic VLDL-TG secretion in obese and lean Zucker rats by the HF diet could be partly explained by decreased exogenous FA availability for VLDL-TG synthesis through its greater channeling toward oxidation and, indirectly, by the altered hepatocyte metabolic state.
authors.affiliation: U177 Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Oussadou
authors.forename: G
authors.initials: G
authors.lastname: Griffaton
authors.forename: A D
authors.initials: AD
authors.lastname: Kalopissis
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000008:administration & dosage*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D008079:Lipoproteins, VLDL