Obesity Attenuates Fasting-Induced Upregulation of Renal Peroxisomal Fatty Acid Oxidation Gene Expression

Increased kidney lipid content during obesity contributes to obesity-related kidney injury but mechanisms of renal lipid accumulation during obesity are incompletely understood. Lean mice also accumulate renal lipid during fasting but how kidney lipid metabolism responds to fasting during obesity is not clear. Mice fed a normal diet (ND) or a high-fat diet (HFD) for 17 weeks underwent either ad libitum feeding (NDfd and HFDfd) or an overnight 16 h fast (NDfa and HFDfa) before measurement of renal lipid and kidney transcriptomics by RNA-seq. Renal triglyceride was increased in NDfa mice compared to NDfd mice and also increased in HFDfd mice compared to NDfd. However HFDfa mice did not have greater renal triglyceride than HFDfd mice. RNA-seq demonstrated increased fatty acid metabolism gene expression in NDfa and HFDfa mice compared to the fed controls, but was significantly greater in NDfa than HFDfa mice. Peroxisomal gene expression was also enriched in NDfa compared to HFDfa mice. Expression of peroxisomal fatty acid oxidation genes Acox1 and Ehhadh, increased in NDfa compared to NDfd, while expression of these genes was not changed in HFDfa compared to HFDfd. These results indicate that obesity blunts fasting-induced peroxisomal fatty acid oxidation gene expression.