Metabolic profiling of livers and blood from obese Zucker rats

Abstract

Obesity frequently leads to changes in fatty acid metabolism with subsequent fatty infiltration in the liver. 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. (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. 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.