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

Hepatic steatosis is associated with mitochondrial oxidative alterations. T his study aimed to characterize in a choline-deficient model of rat fatty l iver whether this oxidative imbalance is related to an impairment of the ca pacity of ATP synthesis both under fed conditions and after starvation, whi ch may sensitize mitochondria to oxidative injury. Mitochondria were isolat ed from normal and fatty livers of fed or 18-hour fasted rats. Oxidative in jury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydry ls. The mitochondrial F0F1-ATP synthase content, tissue ATP concentration, and fiver histology were also determined, Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxi dized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta -F-1 subunit of the F0F1- ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also sign ificantly reduced in fatty liver. Starvation exacerbated mitochondrial oxid ative 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. Th ese data indicate that the mitochondrial oxidative alterations in fatty liv ers are associated with an important reduction of the F0F1-ATP synthase, Th ese changes, which are greatly exacerbated after starvation, may account fo r the reduced synthesis of the hepatic ATP observed in the presence of fatt y infiltration.