Fuel utilization in colonocytes of the rat

Ardawi, M. S. M.; Newsholme, Eric A.

doi:10.1042/bj2310713

Cited by 195 publications

(114 citation statements)

References 41 publications

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“…Indeed, the oxidative capacity of these carcinoma cells at late confluency is similar to what is found in normal isolated colonocytes [27]. Butyrate is considered as a major fuel in normal colonocytes [28,29], however, to the best of our knowledge, no data are available about the capacity of colon carcinoma-derived cells to oxidize this SCFA.…”

Section: Discussionmentioning

confidence: 69%

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Butyrate metabolism upstream and downstream acetyl‐CoA synthesis and growth control of human colon carcinoma cells

Leschelle¹,

Delpal²,

Goubern

et al. 2000

European Journal of Biochemistry

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Butyrate is a short chain fatty acid (SCFA) produced by bacterial fermentation of dietary fibers in the colon lumen which severely affects the proliferation of colon cancer cells in in vitro experiments. Although butyrate is able to interfere with numerous cellular targets including cell cycle regulator expression, little is known about butyrate metabolism and its possible involvement in its effect upon colon carcinoma cell growth. In this study, we found that HT-29 Glc 2/1 cells strongly accumulated and oxidized sodium butyrate without producing ketone bodies, nor modifying oxygen consumption nor mitochondrial ATP synthesis. HT-29 cells accumulated and oxidized sodium acetate at a higher level than butyrate. However, sodium butyrate, but not sodium acetate, reduced cell growth and increased the expression of the cell cycle effector cyclin D3 and the inhibitor of the G1/S cdk-cyclin complexes p21/WAF1/Cip1, demonstrating that butyrate metabolism downstream of acetyl-CoA synthesis is not required for the growth-restraining effect of this SCFA. Furthermore, HT-29 cells modestly incorporated the 14 C-labelled carbon from sodium butyrate into cellular triacylglycerols and phospholipids. This incorporation was greatly increased when d-glucose was present in the incubation medium, corresponding to the capacity of hexose to circulate in the pentose phosphate pathway allowing NADPH synthesis required for lipogenesis. Interestingly, when HT-29 cells were cultured in the presence of sodium butyrate, their capacity to incorporate 14 C-labelled sodium butyrate into triacylglycerols and phospholipids was increased more than twofold. In such experimental conditions, HT-29 cells when observed under an electronic microscope, were found to be characterized by an accumulation of lipid droplets in the cytosol. Our data strongly suggest that butyrate acts upon colon carcinoma cells upstream of acetyl-CoA synthesis. In contrast, the metabolism downstream of acetyl-CoA [i.e. oxidation in the tricarboxylic acid (TCA) cycle and lipid synthesis] likely acts as a regulator of butyrate intracellular concentration.Keywords: butyrate; metabolism; growth; colon carcinoma cells.Epidemiological studies generally suggest a protective role of dietary fibers in colon carcinogenesis [1]. Dietary fibers contained in vegetables, fruit and cereals are heterogeneous group of compounds with different physicochemical properties [2]. They escape digestion and are recovered in the colon lumen. The different proposed mechanisms of action in which fibers may protect against colorectal tumours development include the inactivation of carcinogenic substances, an increase in faecal bulk with shortening of the bowel transit time and a decreased contact time [3]. In the large intestine, fibers can undergo anaerobic fermentation by intestinal flora leading to the production of various metabolites including short chain fatty acids (SCFA, mainly acetate, propionate and butyrate). Among these three, butyrate has received much attention due to its ability to severely ...

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Section: Discussionmentioning

confidence: 69%

“…Indeed, ketone body production represents less than 2% of what is recorded in normal colonocytes [27]. Ketone body have been demonstrated to be used as fuel substrates by normal colonocytes [28].…”

Section: Discussionmentioning

confidence: 99%

Butyrate metabolism upstream and downstream acetyl‐CoA synthesis and growth control of human colon carcinoma cells

Leschelle¹,

Delpal²,

Goubern

et al. 2000

European Journal of Biochemistry

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“…2E) compared with mice consuming the same diet but with the eightmember consortium. Besides short-chain fatty acids, amino acids and ketone bodies (e.g., 3-hydroxybutyrate generated via ketogenesis) serve as respiratory fuels for the gut epithelium (30)(31)(32). GC-MS of cecal contents disclosed that levels of glutamate, cysteine, aspartate, histidine, and 3-hydroxybutyrate were significantly increased in the presence of D. piger (Fig.…”

Section: B Thetaiotaomicron Boosts D Piger Growth In Vitro and In Vivomentioning

confidence: 99%

Metabolic niche of a prominent sulfate-reducing human gut bacterium

Rey¹,

Gonzalez²,

Cheng³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

349

277

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Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high-and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H 2 S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage's substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H 2 -producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H 2 -consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it.artificial human gut microbiota/microbiome | determinants of microbial fitness | hydrogenotrophs | microbial foodwebs | hydrogen sulfide

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“…Colonic carcinoma cells derive energy via metabolism of glucose, whereas normal colonic epithelial cells oxidize butyrate as the key fuel source for cellular proliferation (57)(58)(59). Butyrate has been reported to induce apoptosis in the presence of glucose and pyruvate but promote growth in the absence of these alternative energy sources (60).…”

Section: Cluster C: Metabolismmentioning

confidence: 99%

Quantitative and Temporal Proteome Analysis of Butyrate-treated Colorectal Cancer Cells

Tan¹,

Tan

Lin

et al. 2008

Molecular & Cellular Proteomics

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Colorectal cancer is one of the most common cancers in developed countries, and its incidence is negatively associated with high dietary fiber intake. Butyrate, a shortchain fatty acid fermentation by-product of fiber induces cell maturation with the promotion of growth arrest, differentiation, and/or apoptosis of cancer cells. The stimulation of cell maturation by butyrate in colonic cancer cells follows a temporal progression from the early phase of growth arrest to the activation of apoptotic cascades. Previously we performed two-dimensional DIGE to identify differentially expressed proteins induced by 24-h butyrate treatment of HCT-116 colorectal cancer cells. Herein we used quantitative proteomics approaches using iTRAQ (isobaric tags for relative and absolute quantitation), a stable isotope labeling methodology that enables multiplexing of four samples, for a temporal study of HCT-116 cells treated with butyrate. In addition, cleavable ICAT, which selectively tags cysteine-containing proteins, was also used, and the results complemented those obtained from the iTRAQ strategy. Selected protein targets were validated by real time PCR and Western blotting. A model is proposed to illustrate our findings from this temporal analysis of the butyrateresponsive proteome that uncovered several integrated cellular processes and pathways involved in growth arrest, apoptosis, and metastasis. These signature clusters of butyrate-regulated pathways are potential targets for novel chemopreventive and therapeutic drugs for treatment of colorectal cancer. Molecular & Cellular Proteomics 7:1174 -1185, 2008.In developed countries, colorectal cancer is a prevalent disease with high mortality and morbidity rates (1). This disease has emerged as the top malignancy in Singapore. Environmental factors are responsible for about 80% of the cases, whereas genetic predisposition accounts for the minority 20% of cases. Epidemiological evidence suggests that high intake of dietary fiber reduces the incidence and risk of this neoplasm (2, 3). A wealth of studies has shown that butyrate produced from anaerobic fermentation of indigestible carbohydrate is the molecule responsible for the chemopreventive properties of a fiber-rich diet (4 -6).Although butyrate serves as an energy source for normal colonocytes, in vivo and in vitro studies have shown that at physiological concentrations this natural short-chain fatty acid mediates cell maturation with the promotion of growth arrest followed by differentiation and/or apoptosis of cancer cells (7-11). These biological effects are crucial in colorectal cancer therapy as colonic transformation is characterized by multistage alterations of tissue homeostasis resulting in aberrant cell division and/or cell death (12, 13). Butyrate has been purported as a potential anticancer agent. This initiated notable research in identifying proteins that contribute to its biological effects (14, 15). However, most of these investigations focused on one target at any one time and were thus unable to systematica...

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Fuel utilization in colonocytes of the rat

Cited by 195 publications

References 41 publications

Butyrate metabolism upstream and downstream acetyl‐CoA synthesis and growth control of human colon carcinoma cells

Butyrate metabolism upstream and downstream acetyl‐CoA synthesis and growth control of human colon carcinoma cells

Metabolic niche of a prominent sulfate-reducing human gut bacterium

Quantitative and Temporal Proteome Analysis of Butyrate-treated Colorectal Cancer Cells

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