Butyrate ingestion improves hepatic glycogen storage in the re-fed rat

BACKGROUND: Butyrate naturally produced by intestinal fiber fermentation is the main nutrient for colonocytes, but the metabolic effect of the fraction reaching the liver is not totally known. After glycogen hepatic depletion in the 48-hour fasting rat, we monitored the effect of (butyrate 1.90 mg + glucose 14.0 mg)/g body weight versus isocaloric (glucose 18.2 mg/g) or isoglucidic (glucose 14.0 mg/g) control force-feeding on in vivo changes in hepatic glycogen and ATP contents evaluated ex vivo by NMR in the isolated and perfused liver. RESULTS: The change in glycogen was biphasic with (i) an initial linear period where presence of butyrate in the diet increased (P = 0.05) the net synthesis rate (0.20 ± 0.01 μmol/min.g(-1 )liver wet weight, n = 15) versus glucose 14.0 mg/g only (0.16 ± 0.01 μmol/min.g(-1 )liver ww, n = 14), and (ii) a plateau of glycogen store followed by a depletion. Butyrate delayed the establishment of the equilibrium between glycogenosynthetic and glycogenolytic fluxes from the 6(th )to 8(th )hour post-feeding. The maximal glycogen content was then 97.27 ± 10.59 μmol/g liver ww (n = 7) at the 8(th )hour, which was significantly higher than with the isocaloric control diet (64.34 ± 8.49 μmol/g, n = 12, P = 0.03) and the isoglucidic control one (49.11 ± 6.35 μmol/g liver ww, n = 6, P = 0.003). After butyrate ingestion, ATP content increased from 0.95 ± 0.29 to a plateau of 2.14 ± 0.23 μmol/g liver ww at the 8(th )hour post-feeding (n = 8) [P = 0.04 versus isoglucidic control diet (1.45 ± 0.19 μmol/g, n = 8) but was not different from the isocaloric control diet (1.70 ± 0.18 μmol/g, n = 12)]. CONCLUSION: The main hepatic effect of butyrate is a sparing effect on glycogen storage explained (i) by competition between butyrate and glucose oxidation, glucose being preferentially directed to glycogenosynthesis during the post-prandial state; and (ii) by a likely reduced glycogenolysis from the newly synthesized glycogen. This first demonstration of the improvement of liver glycogen storage by acute butyrate supply may be an important contribution to explaining the beneficial effects on glucose homeostasis of nutritional supply increasing butyrate amount such as fiber diets.