Novel differences in renal gene expression in a diet-induced obesity model

Abstract

Obesity is a significant risk factor for both chronic kidney disease and end-stage renal disease. To better understand disease development, we sought to identify novel genes differentially expressed early in disease progression. We first confirmed that mice fed a high-fat (HF) diet exhibit early signs of renal injury including hyperfiltration. We then performed RNA-Seq using renal cortex RNA from C57BL6/J male mice fed either HF or control (Ctrl) diet. We identified 1,134 genes differentially expressed in the cortex on HF vs. Ctrl, of which 31 genes were selected for follow-up analysis. This included the 9 most upregulated, the 11 most downregulated, and 11 genes of interest (primarily sensory receptors and G proteins). Quantitative (q)RT-PCR for these 31 genes was performed on additional male renal cortex and medulla samples, and 11 genes (including all 9 upregulated genes) were selected for further study based on qRT-PCR. We then examined expression of these 11 genes in Ctrl and HF male heart and liver samples, which demonstrated that these changes are relatively specific to the renal cortex. These 11 genes were also examined in female renal cortex, where we found that the expression changes seen in males on a HF diet are not replicated in females, even when the females are started on the diet sooner to match weight gain of the males. In sum, these data demonstrate that in a HF-diet model of early disease, novel transcriptional changes occur that are both sex specific and specific to the renal cortex.