ARS | Publication request: EFFECTS OF GENDER ON STEATOHEPATITIS IN RATS

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: March 4, 2004
Publication Date: March 4, 2004
Citation: Rivera, C.A., Tcharmtchi, M.H., Ziba, T., Smith, C.W. 2004. Effects of gender on steatohepatitis in rats [abstract]. Journal of Federation of American Societies for Experimental Biology. 18:A661.

Technical Abstract: In a previous study, we reported pathology resembling non-alcoholic steatohepatitis in male rodents exposed to hindlimb unloading, a phenomenon that was not found in endotoxin-resistant rodent strains. Injury was exacerbated when animals were fed a high fat diet. Since females are known to acquire more severe injury than males in other disease processes involving endotoxemia, such as chronic alcohol exposure, it was hypothesized that hindlimb unloading causes more extensive damage in females. In the present study, hepatic injury due to hindlimb unloading (HU) was investigated in male and female Wistar rats fed chow or a diet supplemented with corn oil (20% of calories) and sucrose (50% of calories). After 4 weeks of HU in chow-fed females, <25% of hepatocytes in periportal areas contained cytoplasmic lipid droplets. Hepatocytes in central regions appeared normal, and inflammation was not detected. In contrast, lipid accumulation was observed in approximately 50% of hepatocytes in male rats fed chow. Feeding a high fat/ high sucrose diet during HU markedly increased steatosis in both genders with lipid accumulation in 75-80% of periportal hepatocytes. In males, ballooning hepatocytes and lipid accumulation extended along portal tracts. Several inflammatory foci were also visible in males. Consistent with greater steatosis and inflammation in males, serum ALT activity was approximately 2-fold higher than females. These findings demonstrate that males are more susceptible to the development of steatohepatitis due to HU and dietary fat.