Utilization Of Short-chain Fatty Acids Research Articles

The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

The ecto-5′-nucleotidase (CD73)/adenosine signaling pathway has been reported to regulate tumor epithelial-mesenchymal transition (EMT), migration and proliferation. However, little is known about the metabolic mechanisms underlying its role in trophoblast proliferation and migration. In this study, we aimed to investigate the metabolic role of the CD73/adenosine signaling pathway on the proliferation and migration of trophoblast. We found that CD73 levels were upregulated in preeclamptic placentas compared with the placentas of normotensive pregnant women. EMT and migration of HTR-8/SVneo cells were enhanced when treated with a CD73 inhibitor (100 μM) in vitro. Conversely, excessive adenosine (25 or 50 μM) suppressed trophoblast cell EMT, migration and proliferation. RNA-seq, metabolomics and seahorse findings showed that adenosine treatment resulted in increased expression of PDK1, suppression of aerobic respiration, glycolysis and amino acids synthesis, as well as increased utilization of short-chain fatty acids (SCFAs). Furthermore, the 13C-adenosine isotope tracking experiment demonstrated that adenosine served as a carbon source for the tricarboxylic acid (TCA) cycle. Our results reveal the role of adenosine in regulating trophoblast energy metabolism is like a double-edged sword - either inhibiting aerobic respiration or supplementing carbon sources into metabolic flux. CD73/adenosine signaling regulated trophoblast EMT, migration, and proliferation by modulating energy metabolism. This study indicates that CD73/adenosine signaling potentially plays a role in the occurrence of placenta-derived diseases, including preeclampsia.

Enhanced production of anteiso-branched chain fatty acids rich bacterial oil using Lentibacillus salarius strain BPIITR under furan aldehydes induced oxidative stress

Monomethyl branched-chain fatty acids (mBCFAs) are highly valuable compounds in the oleochemical industry, with diverse industrial applications including pharmaceuticals, biofuels and lubricants. In the current study, the medium components of L. salarius BPIITR were statistically optimized to produce mBCFAs-rich lipid, yielding up to 227.16 ± 16.2 mg/g dcw. The supplementation of 2-methyl butyric acid increased the lipid content to 276.42 ± 7.46 mg/g dcw, with anteiso fatty acids up to 87.59 ± 1.56 % w/w of the total lipid. The addition of 5-hydroxymethyl furfural (5-HmF) and furfural induced oxidative stress, resulting in the synthesis of lipids rich in anteiso-mBCFAs. Furfural supplementation led to a lipid accumulation of 256.49 ± 7.91 mg/g dcw, whereas with 5-HmF, it increased to 284.75 ± 8.98 mg/g dcw. Furthermore, the elongation of mBCFAs from C15:0 to C17:0 was significantly affected during oxidative stress. This study suggests that under oxidative stress conditions, the synthesis of anteiso fatty acids is favored over iso-fatty acids in L. salarius BPIITR. Additionally, value-added products such as trehalose and furan carboxylic acids were identified as potential co-products in this study, with trehalose reaching up to 255.84 ± 8.04, 163.65 ± 20.94, and 217.46 mg/g dcw in the presence of 2-methylbutyric acid, furfural, and 5-HmF, respectively. The concentration of 2-furan carboxylic acid and 2,5-furan dicarboxylic acids in the fermentation broth reached up to 4.37 ± 0.28 g/L and 2.48 ± 0.35 g/L, respectively. The utilization of short-chain fatty acids and furan aldehydes not only provided a cost-effective carbon source but also modulated the metabolic flux towards specific mBCFAs rich bacterial oil production.

Gut dysfunction may be the source of pathological aggregation of alpha-synuclein in the central nervous system through Paraquat exposure in mice

BackgroundOne of the most common types of neurodegenerative diseases (NDDs) is Lewy body disease (LBD), which is characterized by excessive accumulation of α-synuclein (α-syn) in the neurons and affects around 6 million individuals globally. In recent years, due to the environmental factors that can affect the development of this condition, such as exposure to herbicides and pesticides, so it has become a younger disease. Currently, the vast majority of studies on the neurotoxic effects of paraquat (PQ) focus on the late mechanisms of neuronal-glial network regulation, and little is known about the early origins of this environmental factor leading to LBD. ObjectiveTo observe the effect of PQ exposure on intestinal function and to explore the key components of communicating the gut-brain axis by establishing a mouse model. Methods and resultsIn this study, C57BL/6J mice were treated by intraperitoneal injection of 15 mg/kg PQ to construct an LBD time-series model, and confirmed by neurobehavioral testing and pathological examination. After PQ exposure, on the one hand, we found that fecal particle counts and moisture content were abnormal. on the other hand, we found that the expression levels of colonic tight junction proteins decreased, the expression levels of inflammatory markers increased, and the diversity and abundance of gut microbiota altered. In addition, pathological aggregation of α-syn was consistent in the colon and midbrain, and the metabolism and utilization of short-chain fatty acids (SCFAs) were also markedly altered. This suggests that pathological α-syn and SCFAs form the gut may be key components of the communicating gut-brain axis. ConclusionIn this PQ-induced mouse model, gut microbiota disruption, intestinal epithelial barrier damage, and inflammatory responses may be the main causes of gut dysfunction, and pathological α-syn and SCFAs in the gut may be key components of the communicating gut-brain axis.

Polysaccharide, the Active Component of Dendrobium officinale, Ameliorates Metabolic Hypertension in Rats via Regulating Intestinal Flora-SCFAs-Vascular Axis.

Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether Dendrobium officinale polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from Dendrobium officinale. It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of Dendrobium officinale, and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.

Efficient nitrate removal from synthetic groundwater via in situ utilization of short-chain fatty acids from methane bioconversion

Abstract Nitrate (NO3−) removal from groundwater is of great importance since it has posed a major risk to human health. Although methane-based denitrification processes have been developed, the practical application of methane as a carbon source for denitrification is constrained by either a long start-up time or a relatively low nitrate removal rate. This study investigated nitrate removal capacity by using a methane-based membrane biofilm reactor (MBfR) feeding with synthetic groundwater. A high nitrate removal rate of 706 mg-N L−1 d−1 was achieved, which is by far the highest rate reported for methane-based denitrification reactors. Short-chain fatty acids (SCFAs) were detected as products of methane bioconversion, with concentrations of acetic and propionic acid up to 168.8 mg L−1 and 50.2 mg L−1, respectively. Long-term operation and batch test results revealed that the SCFAs generated from methane bioconversion were in situ utilized for supporting nitrate removal as carbon and electron sources, thus leading to a practically useful removal rate. The findings suggest that it is promising to apply the methane-based MBfR to remove nitrate from nitrate contaminated groundwater.

Mitochondrial FgEch1 is responsible for conidiation and full virulence in Fusarium graminearum

Enoyl-CoA hydratase (Ech) is an important and well-recognized enzyme that functions in the degradation of fatty acids by β-oxidation. However, its functions in plant pathogenic fungi are not well known. We characterized an Ech1 orthologue, FgEch1, in Fusarium graminearum. The FgEch1 deletion mutant was defective in the utilization of short-chain fatty acids and conidiation, but not in hyphal growth on glucose-rich media or in perithecium formation. The FgEch1 deletion mutant showed reduced deoxynivalenol (DON) production and virulence in plants. Deletion of FgEch1 also led to increased production of lipid droplets and autophagy. FgEch1, which was localized in the mitochondrion, required the MTS domain for mitochondrial localization and function in F. graminearum. Taken together, these data indicate that mitochondrial FgEch1 is important for conidiation, DON production, and plant infection.

Deletion of mouse Alkbh7 leads to obesity

Mammals have nine homologues of the Escherichia coli AlkB repair protein: Alkbh1-8, and the fat mass and obesity associated protein FTO. In this report, we describe the first functional characterization of mouse Alkbh7. We show that the Alkbh7 protein is located in the mitochondrial matrix and that an Alkbh7 deletion dramatically increases body weight and body fat. Our data indicate that Alkbh7, directly or indirectly, facilitates the utilization of short-chain fatty acids, which we propose is the likely cause for the obesity phenotype observed in the Alkbh7(-/-) mice. Collectively, our data provide the first direct demonstration that murine Alkbh7 is a mitochondrial resident protein involved in fatty acid metabolism and the development of obesity.

System level metabolic effects of a Schistosoma japonicum infection in the Syrian hamster

A metabolic profiling strategy was used to investigate the metabolic responses of Syrian hamsters (SLAC) to a Schistosoma japonicum infection using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy and pattern recognition. In two independent experiments, male hamsters were each infected with 100 S. japonicum cercariae. At days 34–36 post-infection, urine was obtained from hamsters housed individually in metabolism cages. At the same time, urine was collected from age- and sex-matched infection-free control hamsters. The main biochemical effects of a S. japonicum infection in the hamster consisted of reduced levels of urinary tricarboxylic acid cycle intermediates, including citrate and succinate and increased levels of pyruvate. In addition, a range of microbial-related metabolites, such as hippurate, p-cresol glucuronide, phenylacetylglycine and trimethylamine were also associated with a S. japonicum infection. Most of the observed biochemical effects were in common with those previously characterized for a S. mansoni infection in a mouse host. The major distinguishing consequence of a S. japonicum infection in the hamster was the inhibition of manufacture or utilization of short-chain fatty acids, when compared to a S. mansoni infection in the mouse.

Utilization of Short-Chain Fatty Acids by Colonic Mucosal Tissue Strips: A New Method of Assessing Colonic Mucosal Metabolism

Background: Previous metabolic studies of the colonic mucosa have been done using isolated cells or small biopsy specimens. Methods: A new method for assessing the utilization of short-chain fatty acids in human colonic mucosal tissue strips considerably larger than routine samples was evaluated and compared with the method of isolated colonocytes. Human colonic mucosal strips and isolated human and rat colonocytes were incubated with acetate (C2), butyrate (C4), and hexanoate (C6), and oxidation rates obtained by quantifying the production of CO2. Results: The wet weight of strips was highly correlated with the production of CO2, and intersample coefficient of variance was <10%. The production of CO2 from the oxidation of C2, C4, and C6 was in the order of C2 > C4

Effect of dietary fat on the lipid composition and utilization of short‐chain fatty acids by rat colonocytes

The objective of the present studies was to examine the effect of dietary fat on the lipid composition of rat colonocytes and their utilization of short-chain fatty acids (SCFA). Rats were fed 14% beef fat, fish oil or safflower oil plus 2% corn oil in a semi-synthetic base diet for 4 wk. Colonocytes were isolated and their lipid composition was examined. Feeding beef fat and fish oil resulted in an increase in monounsaturated fatty acids and a reduction in omega-6 fatty acids. Feeding fish oil resulted in an enrichment with omega-3 fatty acids. There was no dietary influence on the amount of either cholesterol or phospholipids of colonocytes. Fish oil feeding resulted in significant increase in colonocyte free fatty acids (FFA) as compared to other diets. Dietary fat was found to have no effect on SCFA utilization by colonocytes. Colonocytes were found to utilize SCFA in the order of butyrate greater than or equal to acetate greater than or equal to propionate. The presence of acetate and propionate in the medium had no effect on the rate of butyrate utilization.

The Metabolic Functions of Carnitine in Torulopsis bovina

The carnitine-responsive mutant yeast Torulopsis bovina ATCC 26014, when grown on medium supplemented with carnitine, contained acetyl- and propionylcarnitines, consistent with the presence of carnitine acetyltransferase, which catalyses the reaction carnitine + acyl-CoA ⇌ acylcarnitine + CoA. Two hypotheses for the metabolic function of carnitine were tested. (1) That by reacting with acyl-CoA and releasing CoA, carnitine decreases the requirement for CoA. The effect of carnitine on the growth of the organism was measured in medium containing limiting amounts of pantothenate, which is a component of CoA. Carnitine did not increase the cell yield, suggesting that it did not exert a pantothenate-sparing effect. (2) That carnitine facilitates utilization of short-chain fatty acids. Carnitine reversed the growth inhibition which occurred when acetate was present in the medium, and also increased the respiration rate when acetate was the substrate, results consistent with the hypothesis that the carnitine acetyltransferase system was the limiting factor in transport of acetyl groups into mitochondria of T. bovina ATCC 26014. The properties of the carnitine-responsive strain were compared with those of the wild-type, T. bovina ATCC 22987. Growth rate of the wild-type was rapid and was not stimulated by carnitine, nor was it inhibited by acetate in the growth medium. Acetate increased the respiration rate of the wild-type to the same extent in the presence or absence of carnitine. It is postulated that the mutant lacks a mechanism for handling acetate which is present in the wild-type, and that addition of carnitine to the medium enables the carnitine acetyltransferase system of the mutant to increase the rate of transport of acetyl groups into the mitochondria.