Glucose alleviates ammonia-induced inhibition of short-chain fatty acid metabolism in rat colonic epithelial cells

2003 ◽  
Vol 285 (1) ◽  
pp. G105-G114 ◽  
Author(s):  
John D. Cremin ◽  
Mark D. Fitch ◽  
Sharon E. Fleming

Ammonia decreased metabolism by rat colonic epithelial cells of butyrate and acetate to CO2 and ketones but increased oxidation of glucose and glutamine. Ammonia decreased cellular concentrations of oxaloacetate for all substrates evaluated. The extent to which butyrate carbon was oxidized to CO2 after entering the tricarboxylic acid (TCA) cycle was not significantly influenced by ammonia, suggesting there was no major shift toward efflux of carbon from the TCA cycle. Ammonia reduced entry of butyrate carbon into the TCA cycle, and the proportion of CoA esterified with acetate and butyrate correlated positively with the production of CO2 and ketone bodies. Also, ammonia reduced oxidation of propionate but had no effect on oxidation of 3-hydroxybutyrate. Inclusion of glucose, lactate, or glutamine with butyrate and acetate counteracted the ability of ammonia to decrease their oxidation. In rat colonocytes, it appears that ammonia suppresses short-chain fatty acid (SCFA) oxidation by inhibiting a step before or during their activation. This inhibition is alleviated by glucose and other energy-generating compounds. These results suggest that ammonia may only affect SCFA metabolism in vivo when glucose availability is compromised.

Cytokine ◽  
2000 ◽  
Vol 12 (9) ◽  
pp. 1400-1404 ◽  
Author(s):  
G Pedersen ◽  
T Saermark ◽  
T Horn ◽  
B Giese ◽  
K Bendtzen ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164192 ◽  
Author(s):  
Muhammad Qumar ◽  
Ratchaneewan Khiaosa-ard ◽  
Poulad Pourazad ◽  
Stefanie U. Wetzels ◽  
Fenja Klevenhusen ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Catharina M. C. Mels ◽  
Peet Jansen van Rensburg ◽  
Francois H. van der Westhuizen ◽  
Pieter J. Pretorius ◽  
Elardus Erasmus

Acetylsalicylic acid and/or its metabolites are implicated to have various effects on metabolism and, especially, on mitochondrial function. These effects include both inhibitory and stimulatory effects. We investigated the effect of both combined and separate oral acetylsalicylic acid and acetaminophen administration at therapeutic doses on the urinary metabolite profile of human subjects. In this paper, we provided in vivo evidence, in human subjects, of a statistically significant increase in isobutyrylcarnitine after the administration of a therapeutic dose of acetylsalicylic acid. We, therefore, propose an inhibitory effect of acetylsalicylic acid on the short-chain fatty acid metabolism, possibly at the level of isobutyryl-CoA dehydrogenase.


Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4640-4648 ◽  
Author(s):  
Betty S. Pace ◽  
Gary L. White ◽  
George J. Dover ◽  
Michael S. Boosalis ◽  
Douglas V. Faller ◽  
...  

Orally bioactive compounds that induce γ globin gene expression at tolerable doses are needed for optimal treatment of the β-hemoglobinopathies. Short-chain fatty acids (SCFAs) of 2 to 6 carbons in length induce γ globin expression in animal models, and butyrate, phenylbutyrate, and valproate induce γ globin in human patients. The usefulness of these compounds, however, is limited by requirements for large doses because of their rapid metabolism and their tendency to inhibit cell proliferation, which limits the pool of erythroid progenitors in which γ globin can be induced. Selected short-chain fatty acid derivatives (SCFADs) were recently found to induce γ globin and to stimulate the proliferation of hematopoietic cells in vitro. These SCFADs are now evaluated in vivo in nonanemic transgenic mice containing the human β globin gene locus and in anemic phlebotomized baboons. In mice treated with a SCFAD once daily for 5 days, γ globin mRNA increased 2-fold, reticulocytes increased 3- to 7-fold, and hematocrit levels increased by 27%. Administration of 3 SCFADs in anemic baboons increased F-reticulocytes 2- to 15-fold over baseline and increased total hemoglobin levels by 1 to 2 g/dL per week despite ongoing significant daily phlebotomy. Pharmacokinetic studies demonstrated 90% oral bioavailability of 2 SCFADs, and targeted plasma levels were maintained for several hours after single oral doses equivalent to 10% to 20% of doses required for butyrate. These findings identify SCFADs that stimulate γ globin gene expression and erythropoiesis in vivo, activities that are synergistically beneficial for treatment of the β hemoglobinopathies and useful for the oral treatment of other anemias.


2010 ◽  
Vol 50 (7) ◽  
pp. 605-619 ◽  
Author(s):  
S. Millet ◽  
M. J. Van Oeckel ◽  
M. Aluwé ◽  
E. Delezie ◽  
D. L. De Brabander

Nutrients ◽  
2015 ◽  
Vol 7 (11) ◽  
pp. 8916-8929 ◽  
Author(s):  
Eef Boets ◽  
Lise Deroover ◽  
Els Houben ◽  
Karen Vermeulen ◽  
Sara Gomand ◽  
...  

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