Different Effects of Sodium Butyrate on Hepatic Energy Metabolism

This article [Beauvieux et al., 2008: (http://www.biomedcentral.com/content/pdf/1472-6793-8-19.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/18847460)] shows that the administration of butyrate (1.90 mg butyrate/g bw or 1900 mg/kg bw) and 14 mg/g bw (this is 14 g/kg bw, and I don't know why the doses were given in mg/g bw) to rats increased their liver glycogen concentrations, measured 8 hours after a meal, in comparison to the mean glycogen concentration in rats fed only 14 g/kg bw glucose. That dose of butyrate of 1900 mg/kg bw is like a dose of about 28.2 grams for a 70-kg human [(1900/4.71) x 70 = 28238 mg], and that's a really high dosage of sodium butyrate. Beauvieux et al. (2001) [Beauvieux et al., 2001 (http://jn.nutrition.org/cgi/content/full/131/7/1986)(http://www.ncbi.nlm.nih.gov/pubmed/11435518?dopt=Abstract)] found that infusion of sodium butyrate into the portal vein, so as to maintain relatively high concentrations for prolonged periods of time, impaired energy metabolism, and decreased the intracellular pH in cells (measured in the whole liver, evidently--site unspecified). Those authors (evidently some of the same researchers who did the more recent experiments and article) discuss the fact that butyrate from the colon, according to research cited on the first page), is thought to reach the liver in significant amounts and contribute to energy provision, etc. I've read about that in other articles, but I think it's a much lower concentration. The authors themselves cite research estimating that short-chain fatty acids, including butyrate, are produced by microorganisms, in the colon, at a rate 400-800 mmol/day. The (not sure if this is extracellular or intracellular--I'm assuming intracellular) "cellular" butyrate concentration in the liver is thought to be about 148 uM, normally, according to the authors. I think that using those concentrations for prolonged periods of time is not likely to be physiological, and the concentrations, based on my crude reading of a paper that provides pharmacological data on sodium butyrate in rodents, would probably not be that high, in response to something like 4 g of sodium butyrate, for very long (if they ever reached that concentration). But that article (Beauvieux et al., 2001) is still really good and sheds light on the pH changes produced in response to beta-oxidation.

Those are two possible effects of sodium butyrate, and I think both sets of results have validity. Both of those experiments used either high doses or unusually-prolonged elevations in the butyrate concentrations (0.5 to 5 mM) in the hepatic portal venous blood, but there is the potential, in my opinion, for high doses of sodium butyrate to produce adverse effects on mitochondrial functioning, etc. As the authors of the 2008 paper discuss, however, free fatty acids, such as butyrate, generally do contribute to the replenishment of hepatic glycogen concentrations, in the hours after a meal, in part by decreasing the oxidation of glucose and allowing it to be diverted into glycogen formation.