Hepatic VLDL secretion of genetically obese Zucker rats is inhibited by a high-fat diet. 1996

L Oussadou, and G Griffaton, and A D Kalopissis
U177 Institut National de la Santé et de la Recherche Médicale, Paris, France.

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.

UI MeSH Term Description Entries
D008079 Lipoproteins, VLDL A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues. Pre-beta-Lipoprotein,Prebeta-Lipoprotein,Prebeta-Lipoproteins,Very Low Density Lipoprotein,Very-Low-Density Lipoprotein,Very-Low-Density Lipoproteins,Lipoprotein VLDL II,Lipoproteins, VLDL I,Lipoproteins, VLDL III,Lipoproteins, VLDL1,Lipoproteins, VLDL2,Lipoproteins, VLDL3,Pre-beta-Lipoproteins,Lipoprotein, Very-Low-Density,Lipoproteins, Very-Low-Density,Pre beta Lipoprotein,Pre beta Lipoproteins,Prebeta Lipoprotein,Prebeta Lipoproteins,VLDL Lipoproteins,VLDL1 Lipoproteins,VLDL2 Lipoproteins,VLDL3 Lipoproteins,Very Low Density Lipoproteins
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D011924 Rats, Zucker Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene. Zucker Rat,Zucker Rats,Rat, Zucker
D004041 Dietary Fats Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. Fats, Dietary,Dietary Fat,Fat, Dietary
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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