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Frontiers in Microbiology 2018Recent studies have revealed the feasibility of sodium acetate as a potentially novel inhibitor/stressor relevant to the fermentation from neutralized lignocellulosic... (Review)
Review
Recent studies have revealed the feasibility of sodium acetate as a potentially novel inhibitor/stressor relevant to the fermentation from neutralized lignocellulosic hydrolysates. This mini-review focuses on the toxicity of sodium acetate, which is composed of both sodium and acetate ions, and on the involved cellular responses that it elicits, particularly via the high-osmolarity glycerol (HOG) pathway, the Rim101 pathway, the P-type ATPase sodium pumps Ena1/2/5, and the ubiquitin ligase Rsp5 with its adaptors. Increased understanding of cellular responses to sodium acetate would improve our understanding of how cells respond not only to different stimuli but also to composite stresses induced by multiple components (e.g., sodium and acetate) simultaneously. Moreover, unraveling the characteristics of specific stresses under industrially related conditions and the cellular responses evoked by these stresses would be a key factor in the industrial yeast strain engineering toward the increased productivity of not only bioethanol but also advanced biofuels and valuable chemicals that will be in demand in the coming era of bio-based industry.
PubMed: 30459728
DOI: 10.3389/fmicb.2018.02495 -
International Journal of Molecular... Mar 2023Short-chain fatty acids (SCFAs) are important metabolites of the intestinal flora that are closely related to the development of non-alcoholic fatty liver disease...
Short-chain fatty acids (SCFAs) are important metabolites of the intestinal flora that are closely related to the development of non-alcoholic fatty liver disease (NAFLD). Moreover, studies have shown that macrophages have an important role in the progression of NAFLD and that a dose effect of sodium acetate (NaA) on the regulation of macrophage activity alleviates NAFLD; however, the exact mechanism of action remains unclear. This study aimed to assess the effect and mechanism of NaA on regulating the activity of macrophages. RAW264.7 and Kupffer cells cell lines were treated with LPS and different concentrations of NaA (0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, and 5 mM). Low doses of NaA (0.1 mM, NaA-L) significantly increased the expression of inflammatory factors tumor necrosis factor-α (), interleukin-6 (), and interleukin 1 beta (); it also increased the phosphorylation of inflammatory proteins nuclear factor-κB p65 (NF-κB p65) and c-Jun (), and the M1 polarization ratio of RAW264.7 or Kupffer cells. Contrary, a high concentration of NaA (2 mM, NaA-H) reduced the inflammatory responses of macrophages. Mechanistically, high doses of NaA increased intracellular acetate concentration in macrophages, while a low dose had the opposite effect, consisting of the trend of changes in regulated macrophage activity. Besides, and/or were not involved in the regulation of macrophage activity by NaA. NaA significantly increased total intracellular cholesterol (TC), triglycerides (TG), and lipid synthesis gene expression levels in macrophages and hepatocytes at either high or low concentrations. Furthermore, NaA regulated the intracellular AMP/ATP ratio and AMPK activity, achieving a bidirectional regulation of macrophage activity, in which the PPARγ/UCP2/AMPK/iNOS/IκBα/NF-κB signaling pathway has an important role. In addition, NaA can regulate lipid accumulation in hepatocytes by NaA-driven macrophage factors through the above-mentioned mechanism. The results revealed that the mode of NaA bi-directionally regulating the macrophages further affects hepatocyte lipid accumulation.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Sodium Acetate; NF-kappa B; Lipid Metabolism; AMP-Activated Protein Kinases; Macrophages; Hepatocytes; Lipids; Lipopolysaccharides
PubMed: 36982619
DOI: 10.3390/ijms24065536 -
Animal Nutrition (Zhongguo Xu Mu Shou... Sep 2023Milk yield and composition are critical determining factors for the early growth and development of neonates. The objective of this experiment was to comprehensively...
Milk yield and composition are critical determining factors for the early growth and development of neonates. The objective of this experiment was to comprehensively evaluate the effects of dietary sodium acetate (SA) supplementation on the milk yield and composition of sows and the growth performance of their offspring. A total of 80 sows (Landrace × Yorkshire, 3 to 6 parity) were randomly assigned to 2 groups (with or without 0.1% SA) from d 85 of gestation to d 21 of lactation. The result shows that maternal 0.1% SA supplementation significantly increased sows milk yield, milk fat, immunoglobulin A (IgA) and IgG content in milk ( < 0.05), with the up-regulation of short-chain fatty acids receptors (GPR41 and GPR43) expression and the activation of mammalian target of rapamycin complex C1 (mTORC1) signaling pathway. Consistently, in our in vitro experiment, SA also activated mTORC1 signaling in porcine mammary epithelial cells ( < 0.05). Furthermore, the improvement of milk quality and quantity caused by maternal SA supplementation led to the increase in body weight (BW) and average daily weight gain (ADG) of weaning piglets, with the improvement of gut health and colonization of the beneficial bacteria ( < 0.05). In conclusion, maternal supplementation of 0.1% SA improved the lactation performance (milk yield and milk fat) of sows, possibly with the activation of GPR41/GPR43-mTORC1 signaling. Furthermore, enhanced milk quality improved growth performance, gut health and the colonization of beneficial microbial flora of their piglets.
PubMed: 37484994
DOI: 10.1016/j.aninu.2023.04.003 -
Frontiers in Microbiology 2022The primary product of rumen fermentation is acetic acid, and its sodium salt is an excellent energy source for post-partum cows to manage negative energy balance (NEB)....
The primary product of rumen fermentation is acetic acid, and its sodium salt is an excellent energy source for post-partum cows to manage negative energy balance (NEB). However, it is unknown how adding sodium acetate (NAc) may affect the rumen bacterial population of post-partum cows. Using the identical nutritional total mixed ration (TMR), this research sought to characterize the impact of NAc supplementation on rumen fermentation and the composition of bacterial communities in post-partum cows. After calving, 24 cows were randomly assigned to two groups of 12 cows each: a control group (CON) and a NAc group (ACE). All cows were fed the same basal TMR with 468 g/d NaCl added to the TMR for the CON group and 656 g/d NAc added to the TMR for the ACE group for 21 days after calving. Ruminal fluid was collected before morning feeding on the last day of the feeding period and analyzed for rumen bacterial community composition by 16S rRNA gene sequencing. Under the identical TMR diet conditions, NAc supplementation did not change rumen pH but increased ammonia nitrogen (NH-N) levels and microbial crude protein (MCP) concentrations. The administration of NAc to the feed upregulated rumen concentrations of total volatile fatty acids (TVFA), acetic, propionic, isovaleric and isobutyric acids without affecting the molar ratio of VFAs. In the two experimental groups, the , , and were the dominant rumen phylum, and was the dominant rumen genus. The administration of NAc had no significant influence on the α-diversity of the rumen bacterial community but upregulated the relative abundance of and downregulated the relative abundance of and . In conclusion, the NAc supplementation in the post-peripartum period altered rumen flora structure and thus improved rumen fermentation in dairy cows. Our findings provide a reference for the addition of sodium acetate to alleviate NEB in cows during the late perinatal period.
PubMed: 36478854
DOI: 10.3389/fmicb.2022.1053503 -
Journal of Neuroinflammation Apr 2024Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests...
BACKGROUND
Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear.
METHODS
The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured.
RESULTS
The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis.
CONCLUSIONS
Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.
Topics: Humans; Rats; Animals; Rats, Inbred SHR; Neuroinflammatory Diseases; Hypertension; Blood Pressure; Medulla Oblongata; Microbiota; Acetates
PubMed: 38632579
DOI: 10.1186/s12974-024-03061-3 -
Journal of Dairy Science Nov 2022Acetate supplementation has been shown to increase milk fat yield in diets with low risk of biohydrogenation-induced milk fat depression. The interaction of acetate...
Acetate supplementation has been shown to increase milk fat yield in diets with low risk of biohydrogenation-induced milk fat depression. The interaction of acetate supplementation with specific dietary factors that modify rumen fermentation and short-chain fatty acid (FA) synthesis has not been investigated. The objective of this experiment was to determine the effect of acetate supplemented as sodium acetate at 2 dietary fiber levels. Our hypothesis was that acetate would increase milk fat production more in animals fed the low-fiber diet. Twelve lactating multiparous Holstein cows were arranged in a 4 × 4 Latin square design balanced for carryover effects with a 2 × 2 factorial arrangement of dietary fiber level and acetate supplementation with 21-d experimental periods. The high-fiber diet had 32% neutral detergent fiber and 21.8% starch, and the low-fiber diet had 29.5% neutral detergent fiber and 28.7% starch created by substitution of forages predominantly for ground corn grain. Acetate was supplemented in the diet at an average 2.8% of dry matter (DM) to provide approximately 10 mol/d of acetate as anhydrous sodium acetate. Acetate supplementation increased DM intake by 6%, with no effect on meal frequency or size. Furthermore, acetate supplementation slightly increased total-tract apparent DM digestibility and tended to increase organic matter digestibility. Acetate supplementation increased milk fat concentration and yield by 8.6 and 10.5%, respectively, but there was no interaction with dietary fiber. The increase in milk fat synthesis was associated with 46 and 85 g/d increases in the yield of de novo (<16C) and mixed source (16C) FA, respectively, with no changes in yield of preformed FA (>16C). There was a 9% increase in the concentration of milk mixed-source FA and a 7% decrease in milk preformed FA with acetate supplementation, regardless of dietary fiber level. Acetate supplementation also increased the concentrations of plasma acetate and β-hydroxybutyrate, major metabolic substrates for mammary lipogenesis. Overall, acetate supplementation increased milk fat yield regardless of dietary fiber level through an increase mostly caused by an increase in longer-chain de novo FA, suggesting stimulation of mammary lipogenesis. The heightened mammary de novo lipogenesis was supported by an increase in the concentration of metabolic substrates in plasma.
Topics: Female; Cattle; Animals; Milk; Lactation; Sodium Acetate; Animal Feed; 3-Hydroxybutyric Acid; Detergents; Digestion; Dietary Fiber; Rumen; Diet; Feeding Behavior; Dietary Supplements; Starch
PubMed: 36175230
DOI: 10.3168/jds.2022-21911 -
Frontiers in Microbiology 2022Diarrhea is a word-widely severe disease coupled with gastrointestinal dysfunction, especially in cattle causing huge economic losses. However, the effects of currently...
Sodium acetate/sodium butyrate alleviates lipopolysaccharide-induced diarrhea in mice regulating the gut microbiota, inflammatory cytokines, antioxidant levels, and NLRP3/Caspase-1 signaling.
Diarrhea is a word-widely severe disease coupled with gastrointestinal dysfunction, especially in cattle causing huge economic losses. However, the effects of currently implemented measures are still not enough to prevent diarrhea. Previously we found that dropped short-chain fatty acids in diarrhea yaks, and butyrate is commonly known to be related to the epithelial barrier function and intestinal inflammation. However, it is still unknown whether sodium acetate/sodium butyrate could alleviate diarrhea in animals. The present study is carried out to explore the potential effects of sodium acetate/sodium butyrate on lipopolysaccharide-induced diarrhea in mice. Fifty ICR mice were randomly divided into control (C), LPS-induced (L), and sodium acetate/sodium butyrate (D, B, A)-treated groups. Serum and intestine samples were collected to examine inflammatory cytokines, antioxidant levels, relative gene expressions real-time PCR assay, and gut microbiota changes through high-throughput sequencing. Results indicated that LPS decreased the villus height ( < 0.0001), increased the crypt depth ( < 0.05), and lowered the villus height to crypt depth ratio ( < 0.0001), while sodium acetate/sodium butyrate supplementation caused a significant increase in the villus height ( < 0.001), decrease in the crypt depth ( < 0.01), and increase in the villus height to crypt depth ratio (p < 0.001), especially. In mice treated with LPS, it was found that the serum level of IL-1β, TNF-α ( < 0.001), and MDA ( < 0.01) was significantly higher; however, sodium acetate/sodium butyrate supplementation significantly reduced IL-1β ( < 0.001), TNF-α ( < 0.01), and MDA ( < 0.01), respectively. A total of 19 genera were detected among mouse groups; LPS challenge decreased the abundance of , and , while increased , and in group L. Interestingly, sodium acetate/sodium butyrate supplementation increased , and , while decreased , and . LPS treatment upregulated the expressions of ZO-1 ( < 0.01) and NLRP3 ( < 0.0001) genes in mice; however, sodium acetate/sodium butyrate solution supplementation downregulated the expressions of ZO-1 ( < 0.05) and NLRP3 ( < 0.05) genes in treated mice. Also, the LPS challenge clearly downregulated the expression of Occludin ( < 0.001), Claudin ( < 0.0001), and Caspase-1 ( < 0.0001) genes, while sodium acetate/sodium butyrate solution supplementation upregulated those gene expressions in treated groups. The present study revealed that sodium acetate/sodium butyrate supplementation alleviated LPS-induced diarrhea in mice enriching beneficial bacterium and decreasing pathogens, which could regulate oxidative damages and inflammatory responses NLRP3/Caspase-1 signaling. The current results may give insights into the prevention and treatment of diarrhea.
PubMed: 36386709
DOI: 10.3389/fmicb.2022.1036042 -
Nature Communications Nov 2023Nephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is...
Nephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is essential for determining NPC fate, but the underlying mechanism is unclear. Combining RNA sequencing and quantitative proteomics we identify 267 genes commonly targeted by Wnt activation or glycolysis inhibition in NPCs. Several of the impacted pathways converge at Acetyl-CoA, a co-product of glucose metabolism. Notably, glycolysis inhibition downregulates key genes of the Mevalonate/cholesterol pathway and stimulates NPC differentiation. Sodium acetate supplementation rescues glycolysis inhibition effects and favors NPC maintenance without hindering nephrogenesis. Six2Cre-mediated removal of ATP-citrate lyase (Acly), an enzyme that converts citrate to acetyl-CoA, leads to NPC pool depletion, glomeruli count reduction, and increases Wnt4 expression at birth. Sodium acetate supplementation counters the effects of Acly deletion on cap-mesenchyme. Our findings show a pivotal role of acetyl-CoA metabolism in kidney development and uncover new avenues for manipulating nephrogenesis and preventing adult kidney disease.
Topics: Acetyl Coenzyme A; Sodium Acetate; Nephrons; Kidney; Stem Cells
PubMed: 38007516
DOI: 10.1038/s41467-023-43513-7 -
Toxicology Reports 2021Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned...
Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned uranium mines. Metals including arsenic and uranium co-occur in and around these sites at levels higher than the United States Environmental Protection Agency maximum contaminant levels. To address the potential effect of these metals on the activation of CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to sodium arsenite (1 μM and 10 μM), uranyl acetate (3 μM and 30 μM) or a mixture of sodium arsenite and uranyl acetate (1 μM sodium arsenite + 3 μM uranyl acetate). Sodium arsenite induced a dose dependent effect on activation associated gene expression; targeting immune response genes at the lower dose. Increases in oxidative stress gene expression were observed with both sodium arsenite doses. While uranyl acetate alone did not significantly alter activation associated gene expression, the mixture of uranyl acetate with sodium arsenite demonstrated a combined effect relative to sodium arsenite alone. The results demonstrate the need to investigate metal and metalloid mixtures at environmentally relevant concentrations to better understand the toxicological impact of these mixtures on T-cell activation, function and immune dysregulation.
PubMed: 34926170
DOI: 10.1016/j.toxrep.2021.11.019