Differential effects of short- and long-term high-fat diet feeding on hepatic fatty acid metabolism in rats

Jolita Ciapaite*, Nicole M. van den Broek, Heleen Te Brinke, Klaas Nicolay, Jeroen A. Jeneson, Sander M. Houten, Jeanine J. Prompers

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

64 Citaten (Scopus)


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.

Originele taal-2English
Pagina's (van-tot)441-451
Aantal pagina's11
TijdschriftBiochimica et biophysica acta-Molecular and cell biology of lipids
Nummer van het tijdschrift7-8
StatusPublished - 2011

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