Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats.
BACKGROUND
Butyrate is the main nutrient for the colonocytes but the effect of the fraction reaching the liver is not totally known. A decrease in tissue ATP content and increase in respiration was previously demonstrated when livers were perfused with short-chain fatty acids (SCFA) such as butyrate, or octanoate. In fed rats the oxidative phosphorylation yield was determined on the whole isolated liver perfused with butyrate in comparison with acetate and octoanoate (3 mmol/L). The rate of ATP synthesis was determined in the steady state by monitoring the rate of ATP loss after inhibition of (i) cytochrome oxidase (oxidative phosphorylation) with KCN (2.5 mmol/L) and (ii) glyceraldehyde 3-phosphate dehydrogenase (glycolysis) with IAA (0.5 mmol/L). The ATP flux, estimated by 31P Nuclear Magnetic Resonance, and the measured liver respiration allowed the ATP/O ratio to be determined.


RESULTS
ATP turnover was significantly lower in the presence of butyrate (0.40 +/- 0.10 micromoles/min.g, p = 0.001, n = 7) and octanoate (0.56 +/- 0.10 micromoles/min.g, p = 0.01, n = 5) than in control (1.09 +/- 0.13 micromoles/min.g, n = 7), whereas perfusion with acetate induced no significant decrease (0.76 +/- 0.10 micromoles/min.g, n = 7). Mitochondrial oxygen consumption was unchanged in the presence of acetate (1.92 +/- 0.16 vs 1.86 +/- 0.16 for control) and significantly increased in the presence of butyrate (p = 0.02) and octanoate (p = 0.0004) (2.54 +/- 0.18 and 3.04 +/- 0.15 micromoles/min.g, respectively). The oxidative phosphorylation yield (ATP/O ratio) calculated in the whole liver was significantly lower with butyrate (0.07 +/- 0.02, p = 0.0006) and octanoate (0.09 +/- 0.02, p = 0.005) than in control (0.30 +/- 0.05), whereas there was no significant change with acetate (0.20 +/- 0.02).


CONCLUSIONS
Butyrate or octanoate decrease rather than increase the rate of ATP synthesis, resulting in a decrease in the apparent ATP/O ratio. Butyrate as a nutrient has the same effect as longer chain FA. An effect on the hepatic metabolism should be taken into account when large quantities of SCFA are directly used or obtained during therapeutic or nutritional strategies.
Gallis
Jean-Louis
JL
Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS-UB2, 146 rue Léo Saignat, 33076 F-Bordeaux Cedex, France. jean.louis.gallis@free.fr
Tissier
Pierre
P
Gin
Henri
H
Beauvieux
Marie-Christine
MC
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D002087:Butyrates / Q000493:pharmacokinetics*; D002210:Caprylates / Q000493:pharmacokinetics; D004435:Eating / Q000502:physiology*; D007260:Infusion Pumps; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010759:Phosphorus Isotopes; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
D002087:Butyrates; D002210:Caprylates; D010759:Phosphorus Isotopes; D000255:Adenosine Triphosphate; C031492:octanoic acid