Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status

Hepatology. 2001 Apr;33(4):808-15. doi: 10.1053/jhep.2001.23060.


Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F(0)F(1)-ATP synthase content, tissue ATP concentration, and liver histology were also determined. Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta-F(1) subunit of the F(0)F(1)-ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. In the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic beta-F(1) subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F(0)F(1)-ATP synthase. These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Synthetase Complexes
  • Adenosine Triphosphate / metabolism
  • Animal Nutritional Physiological Phenomena*
  • Animals
  • Energy Metabolism*
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology*
  • Glutathione / metabolism
  • Liver / pathology
  • Male
  • Mitochondria, Liver / metabolism*
  • Mitochondria, Liver / pathology*
  • Multienzyme Complexes / metabolism
  • Oxidation-Reduction
  • Phosphotransferases (Phosphate Group Acceptor) / metabolism
  • Rats
  • Rats, Wistar
  • Reference Values
  • Sulfhydryl Compounds / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism


  • Multienzyme Complexes
  • Sulfhydryl Compounds
  • Thiobarbituric Acid Reactive Substances
  • Adenosine Triphosphate
  • ATP Synthetase Complexes
  • Phosphotransferases (Phosphate Group Acceptor)
  • Glutathione