Short Chain Fatty Acid Regulation of Intestinal Gene Expression

1997 ◽  
pp. 137-144 ◽  
Author(s):  
John A. Barnard ◽  
J. A. Delzell ◽  
N. M. Bulus
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Short Chain

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 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

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.

scholarly journals The Microbe-Derived Short Chain Fatty Acid Butyrate Targets miRNA-Dependent p21 Gene Expression in Human Colon Cancer

PLoS ONE ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. e16221 ◽  
Author(s):  
Shien Hu ◽  
Tien Sy Dong ◽  
Sushila R. Dalal ◽  
Feng Wu ◽  
Marc Bissonnette ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Human Colon ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Human Colon Cancer
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