A metabolic link between mitochondrial ATP synthesis and liver glycogen metabolism: NMR study in rats re-fed with butyrate and/or glucose

作者:Gallis Jean Louis; Gin Henri; Roumes Helene; Beauvieux Marie Christine*
来源:Nutrition & Metabolism, 2011, 8: 38.
DOI:10.1186/1743-7075-8-38

摘要

Background: Butyrate, end-product of intestinal fermentation, is known to impair oxidative phosphorylation in rat liver and could disturb glycogen synthesis depending on the ATP supplied by mitochondrial oxidative phosphorylation and cytosolic glycolysis.
Methods: In 48 hr-fasting rats, hepatic changes of glycogen and total ATP contents and unidirectional flux of mitochondrial ATP synthesis were evaluated by ex vivo (31)P NMR immediately after perfusion and isolation of liver, from 0 to 10 hours after force-feeding with (butyrate 1.90 mg + glucose 14.0 mg.g(-1) body weight) or isocaloric glucose (18.2 mg.g(-1) bw); measurements reflected in vivo situation at each time of liver excision. The contribution of energetic metabolism to glycogen metabolism was estimated.
Results: A net linear flux of glycogen synthesis (similar to 11.10 +/- 0.60 mu mol glucosyl units.h(-1).g(-1) liver wet weight) occurred until the 6(th) hr post-feeding in both groups, whereas butyrate delayed it until the 8(th) hr. A linear correlation between total ATP and glycogen contents was obtained (r(2) = 0.99) only during net glycogen synthesis. Mitochondrial ATP turnover, calculated after specific inhibition of glycolysis, was stable (similar to 0.70 +/- 0.25 mu mol.min(-1).g(-1) liver ww) during the first two hr whatever the force-feeding, and increased transiently about two-fold at the 3(rd) hr in glucose. Butyrate delayed the transient increase (1.80 +/- 0.33 mu mol.min(-1).g(-1) liver ww) to the 6(th) hr post-feeding. Net glycogenolysis always appeared after the 8(th) hr, whereas flux of mitochondrial ATP synthesis returned to near basal level (0.91 +/- 0.19 mu mol.min(-1).g(-1) liver ww).
Conclusion: In liver from 48 hr-starved rats, the energy need for net glycogen synthesis from exogenous glucose corresponds to similar to 50% of basal mitochondrial ATP turnover. The evidence of a late and transient increase in mitochondrial ATP turnover reflects an energetic need, probably linked to a glycogen cycling. Butyrate, known to reduce oxidative phosphorylation yield and to induce a glucose-sparing effect, delayed the transient increase in mitochondrial ATP turnover and hence energy contribution to glycogen metabolism.