The Effects of Short-Chain Fatty Acids on Androstenone Metabolism in Porcine Hepatocytes

The objective of this study was to assess the effects of short-chain fatty acids (SCFAs) on androstenone metabolism and associated gene expression in hepatocytes isolated from intact (boars) and castrated (barrows) male pigs. Isolated porcine hepatocytes were treated with the SCFAs acetate, propionate, and butyrate, both individually and in combination, and then incubated with androstenone. Androstenone metabolism and gene expression were subsequently assessed. Androstenone metabolism was significantly increased by propionate (P < 0.01) and all SCFA combination treatments (P < 0.0001) in hepatocytes from both boars and barrows, and by butyrate in hepatocytes from boars (P = 0.009). Several key genes were upregulated in hepatocytes from barrows; this included AKR1C1 following all SCFA combination treatments (P ≤ 0.01), UGT2A1 and SULT2A1 following treatment with the combination of propionate and butyrate (P < 0.05) and the combination of all three SCFAs (P < 0.05), and SULT1E1 following treatment with the combination of acetate and butyrate (P = 0.005). Short-chain fatty acid treatments did not alter gene expression in hepatocytes from boars; however, plasma levels of estrone-1-sulfate, an abundant testicular steroid in boars, were positively correlated (P < 0.05) with UGT1A1, SULT1E1, and UGT2A1 expression in response to treatment with different SCFAs. These results suggest that SCFA-induced effects on hepatic androstenone metabolism and gene expression depend on the specific SCFA profile and are influenced by testicular steroid hormones.