Hepatic vldl secretion of genetically obese zucker rats is inhibited by a high-fat diet. Oussadou, Larbi, Genevi[grave]eve Griffaton, and Athina-Despina Kalopissis. 1 U177 INSERM and 2 CJF 9508 INSERM, Institut Biom[acute]edical des Cordeliers, 15 rue de l'Ecole de M[acute]edecine, 75270 Paris Cedex 06, France
APStracts 3:0155E, 1996.
Hepatocytes from obese and lean Zucker rats adapted to a control (C) or a high-fat (HF) diet were prepared to study fatty acid (FA) uptake, partition between oxidation and esterification and VLDL production. A first 2h-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, and enhanced 1.4-fold in both genotypes in the presence of 0.7 mM versus 0.1 mM or no oleate. Fat-feeding: a) decreased oleate uptake, esterification, incorporation into VLDL-TG, and mass VLDL-TG secretion; b) 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 1h confirmed that fat-feeding decreased oleate uptake and esterification, greatly stimulating its oxidation and production of acetoacetate (obese) or acetoacetate and -hydroxybutyrate (lean). Lactate and pyruvate syntheses greatly decreased under HF-feeding, remaining higher in obese. 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 channelling towards oxidation, and, indirectly, by the altered hepatocyte metabolic state.

Received 3 January 1996; accepted in final form 26 July 1996.
APS Manuscript Number E4-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996