Histology of liver oxidative stress in an obese mouse model of nonalcoholic fatty liver disease treated with Ω3 fatty acids, TNFα‐receptor blocker, or curcumin (1116.1)

Nonalcoholic fatty liver disease (NAFLD) origins are unclear but progression involves inflammation and correlation with obesity and insulin resistance. Advanced glycation end products (AGEs) are oxidative stress markers that induce inflammation and release reactive oxygen species. AGEs play key roles in the development of vascular inflammation of many types. Tissue accumulation of AGEs is identified by receptor staining (RAGE) . This study evaluated dietary and drug intervention to interrupt RAGE staining in a model of NAFLD. OB/OB leptin knock‐out mice (10/group) received clinical levels of curcumin, Ω3 fatty acids, TNF‐α receptor blocker or control chow for 8 wk. Liver steatosis was scored at 400x. Liver was also stained with PAS for glycoproteins and RAGE antibody. The Image J program was used for quantification of RAGE stain percentage. By H&E, significant reduction of liver fat was seen in groups receiving curcumin or Ω‐3 fatty acids compared to controls. By RAGE stain, interventions reduced AGES from 38.1% (untreated) to 26.4% (TNF blocker) and 26.8% (Ω3). p value, 0.15. This pilot experiment suggests that AGEs contribute to the development of nonalcoholic fatty liver disease and/or the progression of NAFLD to nonalcoholic steatohepatitis. The progression, in our model, is interrupted by food additives or an anti‐inflammatory. Studies to expand this approach to interrupt NAFLD are planned. Grant Funding Source : Funding: St Luke’s Hospital Foundation grant to LA