scholarly journals Short-chain fatty acid synthesis in brain. Subcellular localization and changes during development

1975 ◽  
Vol 152 (3) ◽  
pp. 477-484 ◽  
Author(s):  
G L Reijnierse ◽  
H Veldstra ◽  
C J Van der Ber
Keyword(s):  
Subcellular Localization ◽  
Rat Brain ◽  
Short Chain Fatty Acids ◽  
Acid Synthesis ◽  
Mitochondrial Fraction ◽  
Rate Of Change ◽  
Adult Brain ◽  
Short Chain ◽  
Acetyl Coa

Acetyl-CoA synthase (EC 6.2.1.1), Propionyl-CoA synthase (EC 6.2.1.-) and butyryl-CoA synthase (EC 6.2.1.2) were measured in subcellular fractions prepared by primary and density-gradient fractionation from adult rat brain by a method resulting in recoveries close to 100%. Most of the activity of the three enzymes was recovered in the crude mitochondrial fraction. On subfractionation of this crude mitochondrial fraction with continuous sucrose density gradients, most of the activity of the three enzymes was found at a higher density than NAD+-isocitrate dehydrogenase and at about the same density as glutamate dehydrogenase, confirming earlier reported data for acetyl-CoA synthase. The finding that propionyl-CoA synthase and butyryl-CoA synthase had about the same distribution in the gradients as acetyl-CoA synthase adds support to the hypothesis that mitochondria involved in the metabolism of these short-chain fatty acids (all three of which have been shown to result in a rapid and high labelling of glutamine in vivo) form a distinct subpopulation of the total mitochondrial population. The three synthase activities were found to differ from each other in their rate of change and their subcellular localization during rat brain development. This, in combination with the observation that in gradients of adult brain preparations the three activities did not completely overlap, suggests that the three synthase activities are not present in the same proportion to each other in the same subpopulation (s) of mitochondria in the brain.

Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO
Keyword(s):  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

FURTHER STUDIES ON THE BINDING OF γ-AMINOBUTYRIC ACID BY BRAIN

1967 ◽  
Vol 45 (12) ◽  
pp. 1795-1807 ◽  
Author(s):  
Paula Strasberg ◽  
K. A. C. Elliott
Keyword(s):  
Rat Brain ◽  
Mitochondrial Fraction ◽  
Sodium Ion ◽  
The Other ◽  
Aminobutyric Acid ◽  
Sodium Ions ◽  
Ninhydrin Reaction ◽  
Gaba Content

Factors which can interfere with the paper chromatographic – ninhydrin method for determining γ-aminobutyric acid (GABA) are described. The GABA–ninhydrin reaction does not involve loss of CO2. GABA that is occluded in subcellular particles in plain sucrose homogenates of rat brain does not readily exchange with radioactive GABA in solution. The relevant particles are found mostly in the "mitochondrial fraction". These particles deteriorate with time and manipulations, and tend to lose much of their GABA content. The presence of sodium (but not of potassium, calcium, or magnesium) in the suspending medium allows considerably more GABA to be bound. The extra bound GABA is exchangeable with free labelled GABA. Sodium also promotes some exchange between free and occluded GABA. It is concluded from the present and previous results that in brain in vivo very little GABA exists in a freely diffusing situation. There are two forms of bound GABA. One of these is an occluded or storage form which does not readily exchange with free GABA though exchange is to some extent promoted by sodium ions. The other is a form which occurs only in the presence of sodium ion and is freely exchangeable with GABA in solution.

Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model

1997 ◽  
Vol 272 (4) ◽  
pp. G705-G712 ◽  
Author(s):  
J. M. Mariadason ◽  
D. H. Barkla ◽  
P. R. Gibson
Keyword(s):  
Fatty Acids ◽  
Cell Line ◽  
Antigen Expression ◽  
Short Chain Fatty Acids ◽  
Paracellular Permeability ◽  
Short Chain ◽  
Differentiating Agents ◽  
The Relationship ◽  
Chain Fatty Acids

Control of paracellular permeability in the colonic epithelium is fundamental to its functional competence. This study examines the relationship between physiologically relevant short-chain fatty acids (SCFAs) and paracellular permeability using the Caco-2 cell line model. Butyrate induced a concentration-dependent, reversible increase in transepithelial resistance (TER) that was maximal after 72 h. Butyrate (2 mM) increased TER by 299 +/- 69% (mean +/- SE; n = 5; P < 0.05; t-test) and reduced mannitol flux to 52 +/- 11% (P < 0.05) of control. The effect of butyrate was dependent on protein synthesis and gene transcription but not dependent on its oxidation or activation of adenosine 3',5'-cyclic monophosphate. The other SCFAs, propionate and acetate, also induced a concentration-dependent increase in TER. The effect of butyrate paralleled changes in cellular differentiation, because alkaline phosphatase activity, carcinoembryonic antigen expression, and dome formation were increased. Furthermore, other differentiating agents (dimethyl sulfoxide and retinoic acid) also increased TER. Thus SCFAs reduce paracellular permeability in the Caco-2 cell line, possibly by promotion of a more differentiated phenotype. If such an effect occurs in vivo, it may have ramifications for the biology and pathobiology of colonic mucosa.

scholarly journals Fructo-oligosaccharides lower serum lipid levels and suppress high-fat/high-sugar diet-induced inflammation by elevating serum and gut levels of short-chain fatty acids

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989671
Author(s):  
Renqiang Yu ◽  
Yongxiang Yin ◽  
Minkai Cao ◽  
Danni Ye ◽  
Yinghui Zhang ◽  
...  
Keyword(s):  
Serum Lipid ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Lipid Levels ◽  
High Fat ◽  
Serum Lipid Levels ◽  
Tnf Α

Objective This study aimed to investigate the effects of fructo-oligosaccharides (FOS) on serum lipid levels and to determine the mechanisms underlying these effects and the potential role of inflammation. Methods Male C57BL/6 mice received a normal diet, a high-fat/high-sugar (HFS) diet, or an HFS diet supplemented with 10% FOS for 10 weeks. In vivo intestinal and serum short-chain fatty acid (SCFA) levels were measured by gas chromatography. In vivo serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonaldehyde (MDA) were also measured. Lipid accumulation was visualized. Reactive oxygen species (ROS) generation was evaluated and apoptosis was quantified. Results FOS reversed in vivo HFS-induced lipid accumulation in the liver. An HFS diet increased ALT, AST, TC, TG, and LDL serum levels, decreased HDL serum levels, and increased IL-6, TNF-α, 8-OHdG, and MDA levels. These changes were reduced by FOS. FOS also increased intestinal and serum levels of short chain fatty acids (SCFAs). In vitro, SCFAs ameliorated palmitic acid-induced ROS production and apoptosis of HepG2 cells. Conclusion FOS supplementation lowers serum lipid levels and ameliorates HFS-induced inflammation by upregulating SCFAs.

Su2123 Incorporation of Colonic Derived Short Chain Fatty Acids in Cholesterol: An In Vivo Stable Isotope Study in Humans

2013 ◽  
Vol 144 (5) ◽  
pp. S-564
Author(s):  
Eef Boets ◽  
Els Houben ◽  
Karen Windey ◽  
Vicky De Preter ◽  
Sara V. Gomand ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Stable Isotope ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Isotope Study ◽  
Stable Isotope Study ◽  
Chain Fatty Acids

scholarly journals RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Rna Seq ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

scholarly journals Transacylation as a chain-termination mechanism in fatty acid synthesis by mammalian fatty acid synthetase. Synthesis of butyrate and hexanoate by lactating cow mammary gland fatty acid synthetase

1980 ◽  
Vol 186 (1) ◽  
pp. 287-294 ◽  
Author(s):  
J K Hansen ◽  
J Knudsen
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthetase ◽  
Short Chain Fatty Acids ◽  
Acid Synthesis ◽  
Chain Termination ◽  
Short Chain ◽  
Esterified Fatty Acids ◽  
A Chain

1. Purified cow mammary gland fatty acid synthetase synthesized long-chain unesterified and short-chain esterified fatty acids. 2. A direct relationship was observed between the amount of short-chain products synthesized and the concentration of acetyl-CoA in the incubation medium. 3. The short-chain products were identified as butyryl-CoA and hexanoyl-CoA. 4. Inhibition of the terminating thioester hydrolase of the fatty acid synthetase complex with phenylmethanesulphonyl fluoride did not inhibit the synthesis of short-chain products. 5. It is suggested that the synthesis of short-chain fatty acids involves the reverse of the ‘loading’ reaction.

scholarly journals Prebiotics, Probiotics and Synbiotic for Bone Health

2021 ◽  
Author(s):  
Bolaji Lilian Ilesanmi-Oyelere ◽  
Marlena Cathorina Kruger
Keyword(s):  
Fatty Acids ◽  
Bone Resorption ◽  
Bone Health ◽  
Calcium Absorption ◽  
Osteoclast Differentiation ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Micro Organisms

Prebiotics, probiotics and synbiotics has been shown to enhance calcium absorption, gut and bone health. Probiotics are also known to ferment prebiotics to produce the fermentative substrates such as short chain fatty acids (SCFAs), mainly acetate, butyrate and propionate with the help of beneficial micro-organisms in the gut. The expression of these SCFAs has been associated with the inhibition of osteoclast differentiation and bone resorption both in vitro and in vivo. In this review, we discuss the benefits of SCFAs and ways in which prebiotics and probiotics affect bone health by the reduction of inflammation in the gut and the bone.

scholarly journals Studies on the mitochondrially bound form of rat brain creatine kinase

1978 ◽  
Vol 170 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Robert F. G. Booth ◽  
John B. Clark
Keyword(s):  
Creatine Kinase ◽  
Rat Brain ◽  
Mitochondrial Protein ◽  
Mitochondrial Fraction ◽  
Brain Mitochondria ◽  
Adult Brain ◽  
Reverse Direction ◽  
Total Creatine ◽  
Brain Creatine Kinase ◽  
Brain Energy

1. The development of the total rat brain creatine kinase was studied in brain homogenates. Until approx. 14–15 days after birth, the activity remains less than one-third that of the adult activity (207±6 units/g wet wt. s.d.; n=3). Over the next 10 days the activity increases markedly to the adult value and thereafter remains essentially constant. 2. In the adult brain, approx. 5% (11.9±2.2 units/g wet wt. s.d.; n=5) of the total creatine kinase is associated with the mitochondrial fraction. This creatine kinase could not be solubilized by sodium acetate solutions of up to 0.8m concentration, whereas 66% of the hexokinase associated with brain mitochondria was released under these conditions. 3. Rat brain mitochondria incubated in the presence of various concentrations of creatine (1, 5 and 10mm) and ADP (100μm) synthesized phosphocreatine at rates of approx. 4.5, 11 and 17.5nmol/min per mg of mitochondrial protein. Atractyloside (50μm) or oligomycin (1.5μg/mg of mitochondrial protein) completely inhibited the synthesis of phosphocreatine. 4. The apparent Km and Vmax. values of the mitochondrially bound rat brain creatine kinase were determined in both directions. The Vmax. in the direction of phosphocreatine synthesis is 237nmol/min per mg of mitochondrial protein, with an apparent Km for creatine of 1.67mm and for MgATP2−of 0.1mm, and in the reverse direction Vmax. is 489nmol/min per mg of mitochondrial protein, with an apparent Km for phosphocreatine of 0.4mm and for MgADP−of 27μm. 5. The results are discussed with reference to the role that the mitochondrially bound creatine kinase may play in the development of brain energy metabolism.

scholarly journals Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia

2020 ◽  
Vol 134 (2) ◽  
pp. 289-302 ◽  
Author(s):  
Yanling Chang ◽  
Yunyan Chen ◽  
Qiong Zhou ◽  
Chuan Wang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Phylogenetic Reconstruction ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Pregnant Rats ◽  
Faecal Samples ◽  
G Protein Coupled ◽  
Chain Fatty Acids

Abstract Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.

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