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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)441-451
Number of pages11
JournalBiochimica et biophysica acta-Molecular and cell biology of lipids
Volume1811
Issue number7-8
DOIs
Publication statusPublished - 2011

Keywords

  • Hepatic steatosis
  • Mitochondria
  • Acylcarnitine
  • Fatty acid
  • Stearoyl-CoA desaturase 1
  • Oxidative stress
  • DE-NOVO LIPOGENESIS
  • LIVER-DISEASE
  • MITOCHONDRIAL DYSFUNCTION
  • PROTECTS MICE
  • OXIDATIVE-PHOSPHORYLATION
  • TRANSCRIPTION FACTOR
  • INSULIN-RESISTANCE
  • SKELETAL-MUSCLE
  • COA DESATURASE
  • FEMALE RATS

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