Abstract
BackgroundButyrate, 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.MethodsIn 48 hr-fasting rats, hepatic changes of glycogen and total ATP contents and unidirectional flux of mitochondrial ATP synthesis were evaluated by ex vivo 31P 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.ResultsA net linear flux of glycogen synthesis (~11.10 ± 0.60 μmol glucosyl units.h-1.g-1 liver wet weight) occurred until the 6th hr post-feeding in both groups, whereas butyrate delayed it until the 8th hr. A linear correlation between total ATP and glycogen contents was obtained (r2 = 0.99) only during net glycogen synthesis. Mitochondrial ATP turnover, calculated after specific inhibition of glycolysis, was stable (~0.70 ± 0.25 μmol.min-1.g-1 liver ww) during the first two hr whatever the force-feeding, and increased transiently about two-fold at the 3rd hr in glucose. Butyrate delayed the transient increase (1.80 ± 0.33 μmol.min-1.g-1 liver ww) to the 6th hr post-feeding. Net glycogenolysis always appeared after the 8th hr, whereas flux of mitochondrial ATP synthesis returned to near basal level (0.91 ± 0.19 μmol.min-1.g-1 liver ww).ConclusionIn liver from 48 hr-starved rats, the energy need for net glycogen synthesis from exogenous glucose corresponds 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.
Highlights
Butyrate, end-product of intestinal fermentation, is known to impair oxidative phosphorylation in rat liver and could disturb glycogen synthesis depending on the adenosine triphosphate (ATP) supplied by mitochondrial oxidative phosphorylation and cytosolic glycolysis
A recent in vivo study in human [5] evidenced that short chain fatty acids (SCFA) were released by the gut (34.9 ± 9.1 μmol. kg-1 body weight. h-1) in the circulatory system, while the gut butyrate release was counterbalanced by butyrate hepatic uptake (-3.8 ± 1.6 μmol. kg-1 body weight. h-1)
After 48 hr starvation, the liver glycogen content was undetectable with nuclear magnetic resonance (NMR) (Figure 2) compared to a liver isolated from a control rat fed ad libitum (Figure 3A)
Summary
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. Recent findings in the field of gut microbial flora strongly suggest that the symbiotic relationship between the intestinal microbiota and the human host can influence health [2]. The main site for butyrate metabolism is the liver since hepatic removal close to 100% has been evidenced in Wistar rats adapted to a high-fiber diet [4]. A recent in vivo study in human [5] evidenced that SCFAs were released by the gut This indicated that the liver is highly involved in butyrate metabolism
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