Butyrate impairs energy metabolism in isolated perfused liver of fed rats

This study was designed to test the effects of short-chain fatty acids (SCF A) with an even number of carbon atoms on hepatic energy metabolism. The ef fect of the SCFA was evaluated by measuring liver ATP content and oxygen co nsumption. The ATP content was evaluated using P-31 nuclear magnetic resona nce in isolated liver from fed rats. In addition, respiratory activity (VO2 ) was assessed using Clark electrodes. The livers were perfused with acetat e, butyrate or a medium chain length fatty acid, octanoate, at a concentrat ion of 0.05-5.0 mmol/L. The addition of each substrate enhanced the rate of the net ATP consumption (V-i), establishing a new ATP steady state that re quired a perfusion time of greater than or equal to 20 min, dependent on th e chain length and concentration of the fatty acid (FA). The initial V-i wa s unchanged for acetate and the ATP level stabilized at 58% of the initial level. Both butyrate and octanoate induced a dose-dependent increase in V-i . This may reflect an ATP-consuming process for the intracellular pH regula tion observed during the acidosis associated with the beta -oxidation pathw ay. At the new steady state, the ATP concentration was similar to 45% of th e initial level for both FA. VO2 was both rapidly and reversibly increased, and the change was a function of butyrate or octanoate concentration and o f the chain length. K-m values were similar for butyrate and octanoate. Bec ause all of the effects were similar for butyrate and octanoate, in contras t to acetate, we suggest that the impairment of the energy metabolism by bu tyrate resulted from an increase in the FADH(2)/NADH ratio due to beta -oxi dation. In conclusion, the difference in the hepatic oxidation pathways of two products of intestinal fermentation (acetate and butyrate) explains the ir different actions on energy metabolism.