Metabolic profiling of livers and blood from obese Zucker rats

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.