Metabolic profiling of livers and blood from obese Zucker rats

J Hepatol. 2006 May;44(5):956-62. doi: 10.1016/j.jhep.2005.07.009. Epub 2005 Aug 2.

Abstract

Background/aims: Obesity frequently leads to changes in fatty acid metabolism with subsequent fatty infiltration in the liver.

Methods: In this study, metabolic profile of the livers and blood from lean and obese Zucker rats was established based on quantitative nuclear magnetic resonance spectroscopy (NMR) analysis.

Results: (1)H NMR on liver lipid extracts indicated significantly increased concentrations of total fatty acids and triglycerides. (31)P NMR on liver extracts revealed that obese livers have a compromised energy balance (low [ATP/ADP]) with decreased mitochondrial activity. Simultaneously, increased glycolytic activity was detected. The most pronounced differences were highly increased methionine and decreased betaine concentrations in obese animals. This suggests a significant alteration in methionine metabolism, which may be in part responsible for the development of steatosis, induction of mitochondrial dysfunction, and increased vulnerability of fatty livers to ischemia/reperfusion injury. A trend towards decreased hepatic glutathione concentrations as well as a reduced [PUFA/MUFA] ratio were present in the obese group, indicating increased oxidative stress and lipid peroxidation.

Conclusions: In conclusion, NMR analysis on blood and liver tissue from obese Zucker rats reveals specific metabolic abnormalities in mitochondrial function and methionine metabolism, which result in a decreased hepatic energy state.

MeSH terms

  • Animals
  • Betaine / blood
  • Energy Metabolism / physiology*
  • Fatty Acids, Monounsaturated / metabolism
  • Fatty Acids, Unsaturated / metabolism
  • Fatty Liver / metabolism*
  • Glutathione / metabolism
  • Glycolysis / physiology
  • Lipid Peroxidation / physiology
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Methionine / blood
  • Mitochondria / metabolism
  • Obesity / metabolism*
  • Rats
  • Rats, Zucker
  • Reperfusion Injury / metabolism
  • Triglycerides / blood

Substances

  • Fatty Acids, Monounsaturated
  • Fatty Acids, Unsaturated
  • Triglycerides
  • Betaine
  • Methionine
  • Glutathione