Feeding in sheep during intraportal infusions of short-chain fatty acids and the effect of liver denervation.

1. Castrated male sheep were prepared with cannulae in the hepatic portal vein and jugular vein through which infusions lasting for 3 hr were made. Animals had free access to a pelleted feed the weight of which was continuously recorded so that feeding behaviour could be studied.2. Infusion into the portal vein of a mixture of salts of short-chain fatty acids (acetate, propionate, butyrate: 55, 30, 15) caused a dose-dependent depression in food intake, feeding stopping completely with 4.0 m-mole/min of the mixture. Jugular infusion depressed intake slightly, compared with controls.3. Separate infusions of salts of the three acids showed that the effect of the mixture was due almost entirely to its propionate content; 1.2 m-mole/min of propionate into the portal vein almost completely prevented feeding (39 g eaten per 3 hr) compared with jugular infusion at the same rate (210 g) or no infusion (205 g).4. Surgical sectioning of the hepatic nerve plexus around the wall of the hepatic artery was attempted. Of seven animals which recovered normal food intake, three continued to eat during portal vein infusions of propionate at 1.2 m-mole/min; these sheep were subsequently shown to have been at least 95% denervated. One animal was 50% denervated and ate normally during some infusions but not others. In the remaining three, feeding was suppressed by portal vein infusion of propionate, and these were less than 75% denervated.5. It was concluded that there are receptors in the liver which are sensitive to propionate and which have afferent fibres in the hepatic plexus.