Biological functions of SLC5A8, a candidate tumour suppressor

2005 ◽  
Vol 33 (1) ◽  
pp. 237-240 ◽  
Author(s):  
V. Ganapathy ◽  
E. Gopal ◽  
S. Miyauchi ◽  
P.D. Prasad
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Histone Deacetylases ◽  
Short Chain Fatty Acids ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Short Chain ◽  
Bacterial Fermentation ◽  
Candidate Tumour Suppressor ◽  
Chain Fatty Acids

SLC5A8 is a candidate tumour suppressor gene that is silenced in colon cancer, gastric cancer and possibly other cancers in humans. This gene codes for a transporter belonging to the Na+/glucose co-transporter gene family (SLC5). The cancer-associated silencing of the gene involves hypermethylation of CpG islands present in exon 1 of the gene. SLC5A8 is expressed in colon, ileum, kidney and thyroid gland. The protein coded by the gene mediates the Na+-coupled and electrogenic transport of a variety of monocarboxylates, including short-chain fatty acids, lactate and nicotinate. It may also transport iodide. The normal physiological function of this transporter in the intestinal tract and kidney is likely to facilitate the active absorption of short-chain fatty acids, lactate and nicotinate. One of the short-chain fatty acids that serves as a substrate for SLC5A8 is butyrate. This fatty acid is an inhibitor of histone deacetylases and is known to induce apoptosis in a variety of tumours including colonic tumour. Since butyrate is produced in the colonic lumen at high concentrations by bacterial fermentation of dietary fibre, we speculate that the ability of SLC5A8 to mediate the entry of this short-chain fatty acid into colonic epithelial cells underlies the potential tumour suppressor function of this transporter.

In Silicoandin VitroInteractions between Short Chain Fatty Acids and Human Histone Deacetylases

Biochemistry ◽  
2017 ◽  
Vol 56 (36) ◽  
pp. 4871-4878 ◽  
Author(s):  
Rou Hui Ho ◽  
James Chun Yip Chan ◽  
Hao Fan ◽  
Dorinda Yan Qin Kioh ◽  
Bee Wah Lee ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Histone Deacetylases ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Stimulation of fetal hemoglobin production by short chain fatty acids

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3227-3235 ◽  
Author(s):  
E Liakopoulou ◽  
CA Blau ◽  
Q Li ◽  
B Josephson ◽  
JA Wolf ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Erythroid Cell ◽  
Gamma Globin ◽  
Carbon Fatty Acid ◽  
Chain Fatty Acids

Abstract Butyrate, a four-carbon fatty acid, and its two-carbon metabolic product, acetate, are inducers of gamma-globin synthesis. To test whether other short-chain fatty acids share this property, we first examined whether propionic acid, a three-carbon fatty acid that is not catabolized to acetate, induces gamma-globin expression. Sodium propionate increased the frequency of fetal hemoglobin containing erythroblasts and the gamma/gamma + beta mRNA ratios in adult erythroid cell cultures and F reticulocyte production in a nonanemic juvenile baboon. Short-chain fatty acids containing five (pentanoic), six (hexanoic), seven (heptanoic), eight (octanoic), and nine (nonanoic) carbons induced gamma-globin expression (as measured by increase in gamma-positive erythroblasts and gamma/gamma + beta mRNA ratios) in adult erythroid burst-forming unit cultures. There was a clear-cut relationship between the concentration of fatty acids in culture and the degree of induction of gamma-globin expression. Three-, four-, and five-carbon fatty acids were better inducers of gamma globin in culture as compared with six- to nine-carbon fatty acids. These results suggest that all short-chain fatty acids share the property of gamma-globin gene inducibility. The fact that valproic acid, a derivative of pentanoic acid, also induces gamma-globin expression suggests that short-chain fatty acid derivatives that are already approved for human use may possess the property of gamma-globin inducibility and may be of therapeutic relevance to the beta-chain hemoglobinopathies.

Short-chain fatty acid (SCFA) and medium-chain fatty acid (MCFA) concentrations in human milk consumed by infants born at different gestational ages and the variations in concentration during lactation stages

2020 ◽  
Vol 11 (2) ◽  
pp. 1869-1880 ◽  
Author(s):  
Xinyue Dai ◽  
Tinglan Yuan ◽  
Xinghe Zhang ◽  
Qin Zhou ◽  
Huiya Bi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Human Milk ◽  
Short Chain Fatty Acids ◽  
Term Infant ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Medium Chain ◽  
Naturally Occurring ◽  
Chain Fatty Acids

Short-chain fatty acids and medium-chain fatty acids (4:0, 6:0 and 8:0) are naturally occurring in human milk triacylglycerol and are present in highest amounts in mature full-term infant milk (1.47 ± 0.66 mg g−1 fat).

scholarly journals Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

2020 ◽  
Vol 21 (17) ◽  
pp. 6356 ◽  
Author(s):  
Jin He ◽  
Peiwen Zhang ◽  
Linyuan Shen ◽  
Lili Niu ◽  
Ya Tan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Histone Deacetylases ◽  
Anaerobic Fermentation ◽  
Short Chain Fatty Acids ◽  
Biological Properties ◽  
Short Chain ◽  
Signalling Pathways ◽  
Glucose And Lipid Metabolism ◽  
Chain Fatty Acids

Short-chain fatty acids (SCFAs), particularly acetate, propionate and butyrate, are mainly produced by anaerobic fermentation of gut microbes. SCFAs play an important role in regulating energy metabolism and energy supply, as well as maintaining the homeostasis of the intestinal environment. In recent years, many studies have shown that SCFAs demonstrate physiologically beneficial effects, and the signalling pathways related to SCFA production, absorption, metabolism, and intestinal effects have been discovered. Two major signalling pathways concerning SCFAs, G-protein-coupled receptors (GPRCs) and histone deacetylases (HDACs), are well recognized. In this review, we summarize the recent advances concerning the biological properties of SCFAs and the signalling pathways in inflammation and glucose and lipid metabolism.

scholarly journals Fecal Short-Chain Fatty Acid Concentrations Increase in Newly Paired Male Marmosets (Callithrix jacchus)

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Lifeng Zhu ◽  
Mallory J. Suhr Van Haute ◽  
Haley R. Hassenstab ◽  
Caroline Smith ◽  
Devin J. Rose ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Gut Microbiome ◽  
Short Chain Fatty Acid ◽  
Social Contact ◽  
Common Marmoset ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Chain Fatty Acids

ABSTRACT The role by which the gut microbiome influences host health (e.g., energy equilibrium and immune system) may be partly mediated by short-chain fatty acids, which are bacterial fermentation products from the dietary fibers. However, little is known about longitudinal changes in gut microbiome metabolites during cohabitation alongside social contact. In common marmosets (Callithrix jacchus), the gut microbiome community is influenced by social contact, as newly paired males and females develop convergent microbial profiles. Here, we monitored the dynamics of short-chain fatty acid concentrations in common marmoset feces from the prepairing (PRE) to postpairing (POST) stages. In males, we observed that the concentrations of acetate, propionate, isobutyrate, and isovalerate significantly increased in the POST stage compared to the PRE stage. However, no significant changes were found in females. We further found that the propionate concentration was significantly positively correlated with the abundance of Phascolarctobacterium in the male feces. Thus, the sex difference in the changes in the concentrations of short-chain fatty acids might be related to sex-biased gut microbiome transmission after pairing. We suggest that the significant changes in the gut microbiomes and some short-chain fatty acids of the common marmoset during cohabitation may contribute to physiological homeostasis during pairing. IMPORTANCE This study addressed a knowledge gap about longitudinal changes in the gut microbiome metabolites during animal pairing. This research in the laboratory common marmoset can control for the confounding factors such as diet and other environmental conditions. Phascolarctobacterium showed the highest contribution to the sex-biased transmission of the female to the male after pairing. Here, we observed the sex difference in the increase in short-chain fatty acid concentration in the feces of newly paired marmosets, which may be caused by the sex-biased gut microbiome transmission after pairing.

scholarly journals The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon

2018 ◽  
Vol 315 (1) ◽  
pp. G53-G65 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Maria Buur Nordskov Gabe ◽  
Berit Svendsen ◽  
Lars Ove Dragsted ◽  
Mette Marie Rosenkilde ◽  
...  
Keyword(s):  
Energy Source ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Rat Colon ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Free Fatty Acid Receptors ◽  
Chain Fatty Acids

The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of glucagon like peptide-1 (GLP-1)- and peptide-YY (PYY)-secreting L cells is of great interest because of the potential antidiabetic and antiobesity effects of GLP-1 and PYY. Short-chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate, and butyrate. We show that luminal and especially vascular infusion of acetate and butyrate significantly increases colonic GLP-1 secretion, and to a minor extent also PYY secretion, but only after enhancement of intracellular cAMP. Propionate neither affected GLP-1 nor PYY secretion whether administered luminally or vascularly. A FFAR2- and FFAR3–specific agonist [( S)-2-(4-chlorophenyl)-3,3-dimethyl- N-(5-phenylthiazol-2-yl)butamide (CFMB)/ AR420626 ] had no effect on colonic GLP-1 output, and a FFAR3 antagonist ( AR399519 ) did not decrease the SCFA-induced GLP-1 response. However, the voltage-gated Ca2+-channel blocker nifedipine, the KATP-channel opener diazoxide, and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses. FFAR2 receptor studies confirmed low-potent partial agonism of acetate, propionate, and butyrate, compared with CFMB, which is a full agonist with ~750-fold higher potency than the SCFAs. In conclusion, SCFAs may increase colonic GLP-1/PYY secretion, but FFAR2/FFAR3 do not seem to be involved. Rather, SCFAs are metabolized and appear to function as a colonocyte energy source.NEW & NOTEWORTHY By the use of in situ isolated perfused rat colon we show that short-chain fatty acids (SCFAs) primarily are used as a colonocyte energy source in the rat, subsequently triggering glucagon like peptide-1 (GLP-1) secretion independent of the free fatty acid receptors FFAR2 and FFAR3. Opposite many previous studies on SCFAs and FFAR2/FFAR3 and GLP-1 secretion, this experimental model allows investigation of the physiological interactions between luminal nutrients and secretion from cells whose function depend critically on their blood supply as well as nerve and paracrine interactions.

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