Butyrate Impairs Energy Metabolism in Isolated Perfused Liver of Fed Rats

• Published in: The Journal of nutrition Vol. 131; no. 7; pp. 1986 - 1992
• Main Authors: Beauvieux, Marie-Christine, Tissier, Pierre, Gin, Henri, Canioni, Paul, Gallis, Jean-Louis
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.07.2001; American Society for Nutritional Sciences; American Institute of Nutrition
• Subjects: Acetates - pharmacokinetics; Acetates - pharmacology; Adenosine Triphosphate - metabolism; Animals; Biological and medical sciences; butyrate; Butyrates - pharmacokinetics; Butyrates - pharmacology; Caprylates - pharmacokinetics; Caprylates - pharmacology; Cells, Cultured; Energy Metabolism - drug effects; Fatty Acids, Volatile - pharmacokinetics; Fatty Acids, Volatile - pharmacology; Fundamental and applied biological sciences. Psychology; Hydrogen-Ion Concentration; Intermediate and energetic metabolism; Liver; Liver - drug effects; Liver - metabolism; Magnetic Resonance Spectroscopy; Male; Metabolism; Metabolisms and neurohumoral controls; nuclear magnetic resonance; Oxidation-Reduction; Oxygen Consumption; Perfusion - veterinary; Phosphorus Isotopes; Rats; Rats, Wistar; respiration; Respiratory system; Rodents; short-chain fatty acids; Vertebrates: anatomy and physiology, studies on body, several organs or systems; FID; butyrate; KHB; respiration; NTP; nuclear magnetic resonance; SCFA; pHi; NMR; Vi; Vm; VO2; rats; FA; short-chain fatty acids; Short chain; Energy metabolism; Rat; Digestive system; Liver; Rodentia; Lipids; Oxygen consumption; Fatty acids; Butyrate; Isolated organ; Vertebrata; Mammalia; Animal
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/131.7.1986

This study was designed to test the effects of short-chain fatty acids (SCFA) with an even number of carbon atoms on hepatic energy metabolism. The effect of the SCFA was evaluated by measuring liver ATP content and oxygen consumption. The ATP content was evaluated using 31P nuclear magnetic resonance in isolated liver from fed rats. In addition, respiratory activity (VO2) was assessed using Clark electrodes. The livers were perfused with acetate, butyrate or a medium chain length fatty acid, octanoate, at a concentration of 0.05–5.0 mmol/L. The addition of each substrate enhanced the rate of the net ATP consumption (Vi), establishing a new ATP steady state that required a perfusion time of ≥20 min, dependent on the chain length and concentration of the fatty acid (FA). The initial Vi was unchanged for acetate and the ATP level stabilized at 58% of the initial level. Both butyrate and octanoate induced a dose-dependent increase in Vi. This may reflect an ATP-consuming process for the intracellular pH regulation observed during the acidosis associated with the β-oxidation pathway. At the new steady state, the ATP concentration was ∼45% of the initial level for both FA. VO2 was both rapidly and reversibly increased, and the change was a function of butyrate or octanoate concentration and of the chain length. Km values were similar for butyrate and octanoate. Because all of the effects were similar for butyrate and octanoate, in contrast to acetate, we suggest that the impairment of the energy metabolism by butyrate resulted from an increase in the FADH2/NADH ratio due to β-oxidation. In conclusion, the difference in the hepatic oxidation pathways of two products of intestinal fermentation (acetate and butyrate) explains their different actions on energy metabolism. J. Nutr. 131: 1986–1992, 2001.