Testosterone Deficiency Induces Changes of the Transcriptomes of Visceral Adipose Tissue in Miniature Pigs Fed a High-Fat and High-Cholesterol Diet.

Abstract

Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, S100A9, NCF1 (p47phox), and LEP, were mainly involved in inflammatory response, oxidation-reduction process, and lipid metabolic process, while downregulated genes in CM pigs, i.e., ABHD5, SPP1, and GAS6, were focused on cell differentiation and cell adhesion. Taken together, our study demonstrates that testosterone deficiency alters the expression of numerous genes involved in key biological processes of VAT accumulation under HFC diet and provides a novel genome-wide view on the role of androgen on VAT deposition under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency.