Renal transcriptome changes in testosterone deficient-pigs fed a high-fat diet

Purpose: Obesity and dyslipidemia are associated with increased risk of renal disease.Testosterone deficiency aggravated high-fat diet-induced obesity and hypercholeterolemia. However,whether testosterone deficiency or testosterone deficiency-induced dyslipidemia aggravate the progression of renal disease is not clear. To gain insight into the role of testosterone in modulating renal lipid metabolism, we profiled renal gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT). Methods: Sexually mature male miniature pigs were either surgical castrated or sham-operated, and castrated with testosterone replacement. We administrated to pigs a high-fat and high-cholesterol (HFC) diet for twelve weeks. RNA-Seq was employed to profile renal gene expression in pigs with different testosterone levels. Conclusions: This study demonstrated that testosterone deficiency aggravated renal lipid accumulation in pigs fed an HFC diet and that these effects could be reversed by testosterone replacement therapy. Impaired metabolic processes, bile acid secretion,estrogen signaling pathway and enhanced triglyceride synthesis may contribute to the increased renal lipid accumulation induced by testosterone deficiency and an HFC diet. Renal mRNA profiles of intact male pigs fed a HFC diet (IM), castrated male pigs fed a HFC diet (CM) ,and castrated male pigs treated with testosterone (CMT) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.