Effects of oral butyrate application on insulin signaling in various tissues of chickens.

The influence of butyrate on insulin signaling in chickens was studied because butyrate is produced during microbial fermentation in the large intestine of birds, and butyrate is widely used as a feed additive in animal production. Ross 308 broiler chickens received a daily intraingluvial bolus of sodium butyrate (0.25 g/kg body weight) on days 20-24 of life (n = 10). Plasma butyrate concentration increased after receiving oral butyrate treatment (P < 0.001). Oral butyrate application was associated with decreased protein expression of insulin receptor β subunit (IRβ) in liver (P = 0.008) and both abdominal (P = 0.003) and subcutaneous adipose tissue (P < 0.001), but with elevated IRβ expression in muscle (P = 0.045), assessed by Western blotting. The quantity of hepatic phosphatidyl-inositol-3-kinase was reduced in the butyrate-treated group (P = 0.007); further, mammalian target of rapamycin was downregulated by butyrate in liver (P < 0.001) and subcutaneous adipose tissue (P = 0.038). Oral butyrate application provoked reduced systemic insulin sensitivity in chickens, indicated by elevated fasting blood glucose and subsequently, insulin level. However, responses of insulin signaling cascade to butyrate were tissue specific, suggesting that butyrate could act on glucose shifting among tissues by selectively increasing the glucose uptake of skeletal muscle via IRβ upregulation.