A Combination of Mitochondrial Oxidative Stress and Excess Fat/Calorie Intake Accelerates XXXX by Enhancing Hepatic CC Chemokine Production in @entity19 .

@entity82 @entity13945 @entity66 @entity1560 @entity19 @entity4588 @entity26 @entity3403 @entity969 @entity1561 @entity1575 @entity99 @entity165
UNASSIGNED: Mitochondrial oxidative stress is considered as a key accelerator of @entity82 in various organs including the liver. However, the production of oxidative stress and progression of @entity1575 may merely represent the independent consequences of @entity99 caused by the @entity66 . Because of a lack of appropriate experimental models to evaluate the sole effects of oxidative stress, it is virtually unknown whether this stress is causatively linked to the progression of @entity1575 . Here, we examined the direct effects of mitochondrial reactive @entity26 species (ROS) on the progression of high fat/calorie diet-induced @entity1560 using Tet-mev-1 @entity19 , in which a mutated @entity4588 dehydrogenase transgene impairs the mitochondrial electron transport and generates an excess amount of ROS in response to @entity3403 administration. Wild type and Tet-mev-1 @entity19 that had been continuously given @entity3403 -containing water were subsequently fed either normal chow or a @entity165 -free high-fat/high- @entity969 diet for 4 months at approximately 1 or 2 years of age. Histopathological examinations indicated that neither the mitochondrial ROS induced in Tet-mev-1 @entity19 nor the feeding of wild type animals with high-fat/high- @entity969 diet alone caused significant @entity1575 . Only when the Tet-mev-1 @entity19 were fed a high-fat/high- @entity969 diet, it induced lipid peroxidation in hepatocytes and enhanced hepatic CC chemokine expression. These events were accompanied by increased infiltration of @entity13945 -positive cells and activation of myofibroblasts, resulting in extensive @entity1575 . Interestingly, this combinatorial effect of mitochondrial ROS and excess fat/calorie intake on @entity1575 was observed only in 2-year-old Tet-mev-1 @entity19 , not in the 1-year-old animals. Collectively, these results indicate that mitochondrial ROS in combination with excess fat/calorie intake accelerates @entity1575 by enhancing CC chemokine production in aged animals. We have provided a good experimental model to explore how high fat/calorie intake increases the susceptibility to @entity1561 in aged individuals who have impaired mitochondrial adaptation.
