1. Differential effects of short- and long-term high-fat diet feeding on hepatic fatty acid metabolism in rats
- Author
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Jeroen A. L. Jeneson, Klaas Nicolay, Jeanine J. Prompers, Heleen te Brinke, Jolita Ciapaite, Sander M. Houten, Nicole M. A. van den Broek, Faculteit Medische Wetenschappen/UMCG, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, and Paediatric Metabolic Diseases
- Subjects
Male ,Hepatic steatosis ,Time Factors ,PROTECTS MICE ,Mitochondria, Liver ,Protein oxidation ,SDG 3 – Goede gezondheid en welzijn ,Lipid peroxidation ,chemistry.chemical_compound ,Acylcarnitine ,Non-alcoholic Fatty Liver Disease ,OXIDATIVE-PHOSPHORYLATION ,TRANSCRIPTION FACTOR ,Stearoyl-CoA desaturase 1 ,chemistry.chemical_classification ,INSULIN-RESISTANCE ,Fatty Acids ,Mitochondria ,Liver ,Lipogenesis ,SKELETAL-MUSCLE ,medicine.medical_specialty ,MITOCHONDRIAL DYSFUNCTION ,Biology ,Oxygen Consumption ,SDG 3 - Good Health and Well-being ,LIVER-DISEASE ,FEMALE RATS ,Carnitine ,Internal medicine ,COA DESATURASE ,medicine ,Animals ,Obesity ,Rats, Wistar ,Molecular Biology ,DE-NOVO LIPOGENESIS ,Fatty acid metabolism ,Fatty acid ,Lipid metabolism ,Cell Biology ,Lipid Metabolism ,Dietary Fats ,Rats ,Fatty Liver ,Endocrinology ,chemistry ,Mitochondrial biogenesis ,Oxidative stress ,Lipid Peroxidation ,Stearoyl-CoA desaturase-1 - Abstract
Imbalance in the supply and utilization of fatty acids (FA) is thought to contribute to intrahepatic lipid (IHL) accumulation in obesity. The aim of this study was to determine the time course of changes in the liver capacity to oxidize and store FA in response to high-fat diet (HFD). Adult male Wistar rats were fed either normal chow or HFD for 2.5 weeks (short-term) and 25 weeks (long-term). Short-term HFD feeding led to a 10% higher palmitoyl-t-carnitine-driven ADP-stimulated (state 3) oxygen consumption rate in isolated liver mitochondria indicating up-regulation of 13-oxidation. This adaptation was insufficient to cope with the dietary FA overload, as indicated by accumulation of long-chain acylcarnitines, depletion of free carnitine and increase in FA content in the liver, reflecting IHL accumulation. The latter was confirmed by in vivon14 magnetic resonance spectroscopy and Oil Red 0 staining. Long-term HFD feeding caused further up-regulation of mitochondrial beta-oxidation (24% higher oxygen consumption rate in state 3 with palmitoyl-t-carnitine as substrate) and stimulation of mitochondrial biogenesis as indicated by 62% higher mitochondrial DNA copy number compared to controls. These adaptations were paralleled by a partial restoration of free carnitine levels and a decrease in long-chain acylcarnitine content. Nevertheless, there was a further increase in IHL content, accompanied by accumulation of lipid peroxidation and protein oxidation products. In conclusion, partially effective adaption of hepatic FA metabolism to long-term HFD feeding came at a price of increased oxidative stress, caused by a combination of higher FA oxidation capacity and oversupply of FA. (C) 2011 Elsevier B.V. All rights reserved.
- Published
- 2011