Peroxisomes and mitochondria are dysfunctional in obese diabetic (db/db) mice with fatty liver

Major causes of lipid accumulation in liver are increased import, synthesis or decreased catabolism of fatty acids. The latter is caused by dysfunction of cellular organelle controlling energy homeostasis, i.e. mitochondria. However, peroxisomes appear to be an important organelle in lipid metabolism of hepatocytes, but little is known about their role in the development of non-alcoholic fatty liver disease (NAFLD). To investigate the role of peroxisomes next to mitochondria in excessive hepatic lipid accumulation we used the leptin resistant db/db mice on C57BLKS background, a mouse model that develops hyperphagia induced diabetes with obesity and NAFLD. We used microarrays to determine differences in hepatic gene expression in a mouse model for NAFDL (BKS.Cg-Leprdb (db/db)) and their wildtype littermates C57BL/KSlepr+/+ (BKS) to determine the effect of persistent hepatic lipid accumulation. C57BL/KSlepr+/+ (BKS) and BKS.Cg-Leprdb (db/db) mice (litermates) were kept under standadized conditions with regular chow until db/db mice develop the diabetes and obesitiy phenotype with NAFLD (14 weeks of age).