Hydroxamide derivatives of short-chain fatty acid have erythropoietic activity and induce γ gene expression in vivo

2005 ◽  
Vol 33 (12) ◽  
pp. 1443-1449 ◽  
Author(s):  
Hua Cao ◽  
Manfred Jung ◽  
George Stamatoyannopoulos
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Erythropoietic Activity ◽  
Derivatives Of

scholarly journals Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Globin Gene ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Pharmacokinetic Studies ◽  
Fatty Acid Derivatives ◽  
Globin Gene Expression

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.

scholarly journals Evidence of In Vivo Absorption of Lactate and Modulation of Short Chain Fatty Acid Absorption from the Reticulorumen of Non-Lactating Cattle Fed High Concentrate Diets

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164192 ◽  
Author(s):  
Muhammad Qumar ◽  
Ratchaneewan Khiaosa-ard ◽  
Poulad Pourazad ◽  
Stefanie U. Wetzels ◽  
Fenja Klevenhusen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Acid Absorption ◽  
In Vivo Absorption ◽  
Fatty Acid Absorption

scholarly journals Increased Excretion of C4-Carnitine Species after a Therapeutic Acetylsalicylic Acid Dose: Evidence for an Inhibitory Effect on Short-Chain Fatty Acid Metabolism

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
Keyword(s):  
Fatty Acid ◽  
Acetylsalicylic Acid ◽  
Fatty Acid Metabolism ◽  
Short Chain Fatty Acid ◽  
Acid Metabolism ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Chain Fatty Acid ◽  
Short Chain

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.

scholarly journals Microvesicular Steatosis Induced by a Short Chain Fatty Acid: Effects on Mitochondrial Function and Correlation with Gene Expression

2004 ◽  
Vol 32 (2_suppl) ◽  
pp. 19-25 ◽  
Author(s):  
Robert A. Jolly ◽  
Rita Ciurlionis ◽  
David Morfitt ◽  
Mary Helgren ◽  
Reid Patterson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Mitochondrial Function ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Microvesicular Steatosis

Prediction of In Vivo Short-Chain Fatty Acid Production in Hindgut Fermenting Mammals: Problems and Pitfalls

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

scholarly journals Quantification of in Vivo Colonic Short Chain Fatty Acid Production from Inulin

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

scholarly journals Deletion of atoR from Streptococcus pyogenes Results in Hypervirulence in a Mouse Model of Sepsis and is LuxS Independent

2017 ◽  
Vol 66 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Izabela Sitkiewicz ◽  
James M. Musser
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Mouse Model ◽  
Fatty Acid Metabolism ◽  
Short Chain Fatty Acid ◽  
Acid Metabolism ◽  
Bacterial Species ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Streptococcal Toxic Shock Syndrome

Group A Streptococcus (GAS) is a Gram-positive human pathogen that causes a variety of diseases ranging from pharyngitis to life-threatening streptococcal toxic shock syndrome. Recently, several global gene expression analyses have yielded extensive new information regarding the regulation of genes encoding known and putative virulence factors in GAS. A microarray analysis found that transcription of the GAS gene M5005_Spy_1343 was significantly increased in response to interaction with human polymorphonuclear leukocytes. M5005_Spy_1343 is predicted to encode a member of the LysR family of transcriptional regulators and is located upstream of a putative operon containing six genes. Five of these genes have sequence similarity to genes involved in short-chain fatty acid metabolism, whereas the sixth gene (luxS) is found in many bacterial species and is involved in quorum sensing. Unexpectedly, inactivation of the M5005_Spy_1343 gene resulted in hypervirulence in an intraperitoneal mouse model of infection. Increased virulence was not due to changes in luxS gene expression. We postulate that short-chain fatty acid metabolism is involved in GAS pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document