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Neurogastroenterology and Motility Dec 2018Propionate exhibits affinity for free fatty acid receptor 2 (FFA2, formerly GPR43) and FFA3 (GPR41). These two G protein-coupled receptors (GPCRs) are expressed by...
BACKGROUND
Propionate exhibits affinity for free fatty acid receptor 2 (FFA2, formerly GPR43) and FFA3 (GPR41). These two G protein-coupled receptors (GPCRs) are expressed by enteroendocrine L cells that contain anorectic peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), while FFA3 is also expressed by enteric neurons. Few studies have investigated the individual roles of FFA2 and FFA3 in propionate's gastrointestinal (GI) effects. Here, we compared FFA2, FFA3, and propionate mucosal responses utilizing selective ligands including an FFA3 antagonist, in mouse and human colonic mucosa.
METHODS
Vectorial ion transport was measured in native colonic preparations from normal mouse and human colon with intact submucosal innervation. Endogenous fecal pellet propulsion was monitored in colons isolated from wild-type (WT) and PYY-/- mice.
KEY RESULTS
FFA2 and FFA3 signaling differed significantly. FFA2 agonism involved endogenous L cell-derived PYY and was glucose dependent, while FFA3 agonism was independent of PYY and glucose, but required submucosal enteric neurons for activity. Tonic FFA3 activity was observed in mouse and human colon mucosa. Apical propionate responses were a combination of FFA2-PYY mediation and FFA3 neuronal GLP-1- and CGRP-dependent signaling in mouse ascending colon mucosa. Propionate also slowed WT and PYY-/- colonic transit, and this effect was blocked by a GLP-1 receptor antagonist.
CONCLUSIONS & INFERENCES
We conclude that luminal propionate costimulates FFA2 and FFA3 pathways, reducing anion secretion and slowing colonic motility; FFA2 via PYY mediation and FFA3 signaling by activation of enteric sensory neurons.
Topics: Animals; Colon; Female; Humans; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Middle Aged; Propionates; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 30136343
DOI: 10.1111/nmo.13454 -
Biomolecules Jun 2023Coproheme decarboxylases (ChdCs) are terminal enzymes of the coproporphyrin-dependent heme biosynthetic pathway. In this reaction, two propionate groups are cleaved from...
Coproheme decarboxylases (ChdCs) are terminal enzymes of the coproporphyrin-dependent heme biosynthetic pathway. In this reaction, two propionate groups are cleaved from the redox-active iron-containing substrate, coproheme, to form vinyl groups of the heme product. The two decarboxylation reactions proceed sequentially, and a redox-active three-propionate porphyrin, called monovinyl, monopropionate deuteroheme (MMD), is transiently formed as an intermediate. While the reaction mechanism for the first part of the redox reaction, which is initiated by hydrogen peroxide, has been elucidated in some detail, the second part of this reaction, starting from MMD, has not been studied. Here, we report the optimization of enzymatic MMD production by ChdC and purification by reversed-phase chromatography. With the obtained MMD, we were able to study the second part of heme formation by actinobacterial ChdC from , starting with Compound I formation upon the addition of hydrogen peroxide. The results indicate that the second part of the decarboxylation reaction is analogous to the first part, although somewhat slower, which is explained by differences in the active site architecture and its H-bonding network. The results are discussed in terms of known kinetic and structural data and help to fill some mechanistic gaps in the overall reaction catalyzed by ChdCs.
Topics: Hydrogen Peroxide; Propionates; Heme; Carboxy-Lyases
PubMed: 37371526
DOI: 10.3390/biom13060946 -
Scientific Reports Dec 20233-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA),...
3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41.
Topics: Animals; Humans; Lipid Metabolism; Hempa; Liver; Propionates
PubMed: 38040866
DOI: 10.1038/s41598-023-48525-3 -
International Journal of Molecular... Sep 2022Short-chain fatty acids (SCFAs) are potent immune modulators present in the gingival crevicular fluid. It is therefore likely that SCFAs exert a role in periodontal...
Short-chain fatty acids (SCFAs) are potent immune modulators present in the gingival crevicular fluid. It is therefore likely that SCFAs exert a role in periodontal health and disease. To better understand how SCFAs can module inflammation, we screened acetic acid, propionic acid, and butyric acid for their potential ability to lower the inflammatory response of macrophages, gingival fibroblasts, and oral epithelial cells in vitro. To this end, RAW 264.7 and primary macrophages were exposed to LPSs from with and without the SCFAs. Moreover, gingival fibroblasts and HSC2 oral epithelial cells were exposed to IL1β and TNFα with and without the SCFAs. We report here that butyrate was effective in reducing the lipopolysaccharide (LPS)-induced expression of IL6 and chemokine (C-X-C motif) ligand 2 (CXCL2) in the RAW 264.7 and primary macrophages. Butyrate also reduced the IL1β and TNFα-induced expression of IL8, chemokine (C-X-C motif) ligand 1 (CXCL1), and CXCL2 in gingival fibroblasts. Likewise, butyrate lowered the induced expression of CXCL1 and CXCL2, but not IL8, in HSC2 cells. Butyrate further caused a reduction of p65 nuclear translocation in RAW 264.7 macrophages, gingival fibroblasts, and HSC2 cells. Propionate and acetate partially lowered the inflammatory response in vitro but did not reach the level of significance. These findings suggest that not only macrophages, but also gingival fibroblasts and oral epithelial cells are susceptive to the anti-inflammatory activity of butyrate.
Topics: Acetates; Anti-Inflammatory Agents; Butyric Acid; Chemokine CXCL1; Chemokine CXCL2; Fatty Acids, Volatile; Interleukin-6; Lipopolysaccharides; Propionates; Tumor Necrosis Factor-alpha
PubMed: 36232340
DOI: 10.3390/ijms231911006 -
Poultry Science Jan 2024The objective of this study was to evaluate the effects of dietary chromium (Cr), as Cr propionate (Cr Prop), on measures of insulin sensitivity in turkeys. Plasma...
The objective of this study was to evaluate the effects of dietary chromium (Cr), as Cr propionate (Cr Prop), on measures of insulin sensitivity in turkeys. Plasma glucose and nonesterified fatty acid (NEFA), and liver glycogen concentrations were used as indicators of insulin sensitivity. One-day-old Nicholas Large White female poults (n = 336) were randomly assigned to dietary treatments consisting of 0 (control), 0.2, 0.4, or 0.6 mg supplemental Cr/kg diet. Each treatment consisted of 12 replicate cages with 7 turkeys per cage. Final BW were taken on d 34, and on d 35 two birds from each cage were sampled for plasma glucose and NEFA, and liver glycogen determination at the initiation (fed state) and termination (fasted state) of a 24-h fast. Following a 24-h fast, 2 turkeys per cage were refed (refed state) their treatment diet for 4 h, and then harvested. Feed/gain and ADG did not differ between control and Cr-supplemented turkeys over the 34-d study, but feed intake tended (P = 0.071) to be greater for controls than turkeys receiving 0.4 mg Cr/kg diet. Fed turkeys had greater plasma glucose (P = 0.002) and liver glycogen (P = 0.001) concentrations, and lower (P = 0.001) NEFA concentrations than fasted birds. Turkeys refed after fasting had greater (P = 0.001) plasma glucose and liver glycogen concentrations, and lower (P = 0.001) plasma NEFA levels than fed turkeys. Liver glycogen and plasma NEFA concentrations did not differ among control and Cr-supplemented birds in the fed, fasted, or refed state. Plasma glucose concentrations were not affected by treatment in fed or fasted turkeys. Turkeys supplemented with 0.2 or 0.4 mg Cr/kg and refed after fasting had lower (quadratic, P = 0.038) plasma glucose concentrations than controls. Plasma glucose concentrations in refed birds did not differ among Cr-supplemented turkeys. The lower plasma glucose concentration in Cr-supplemented turkeys following refeeding is consistent with Cr enhancing insulin sensitivity.
Topics: Animals; Female; Insulin Resistance; Blood Glucose; Propionates; Turkeys; Liver Glycogen; Fatty Acids, Nonesterified; Chickens
PubMed: 37992621
DOI: 10.1016/j.psj.2023.103215 -
Nutrients Mar 2022Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate...
Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.
Topics: Animals; Autistic Disorder; Biotin; Propionates; Rats; Rats, Wistar
PubMed: 35334937
DOI: 10.3390/nu14061280 -
BMJ Open Diabetes Research & Care Jul 2021Propionic acid (PA) is a common food preservative generally recognized as safe by the US Food and Drug Administration; however, exogenous PA has effects on glucose... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Propionic acid (PA) is a common food preservative generally recognized as safe by the US Food and Drug Administration; however, exogenous PA has effects on glucose metabolism that are not fully understood. Our preclinical studies demonstrated exogenous PA increases glucagon, norepinephrine, and endogenous glucose production (EGP).
RESEARCH DESIGN AND METHODS
We performed a randomized, placebo-controlled, crossover study in 28 healthy men and women to determine the effect of PA (1500 mg calcium propionate) on these factors. Subjects had two study visits, each preceded by a 1 week, PA-free diet. During each visit, glucose, insulin, glucagon, norepinephrine, epinephrine, and EGP were assessed for 2 hours after oral administration of PA/placebo under resting conditions (protocol 1) and during either a euglycemic (~85-90 mg/dL) or hypoglycemic (~65-70 mg/dL) hyperinsulinemic clamp (protocol 2).
RESULTS
PA, as compared with placebo, significantly increased: (1) glucagon and norepinephrine during protocol 1; (2) glucagon, norepinephrine, and epinephrine under euglycemic conditions in protocol 2; and (3) norepinephrine, epinephrine, and EGP under hypoglycemic conditions in protocol 2.
CONCLUSION
Oral consumption of PA leads to inappropriate activation of the insulin counterregulatory hormonal network. This inappropriate stimulation highlights PA as a potential metabolic disruptor.
Topics: Blood Glucose; Cross-Over Studies; Female; Food Preservatives; Glucose; Glucose Clamp Technique; Humans; Male; Propionates; United States
PubMed: 34312159
DOI: 10.1136/bmjdrc-2021-002336 -
Journal of Agricultural and Food... Sep 2022In this study, the complex volatilome of maize silage samples conserved for 229 d, inoculated with () and (), is explored by means of advanced fingerprinting...
In this study, the complex volatilome of maize silage samples conserved for 229 d, inoculated with () and (), is explored by means of advanced fingerprinting methodologies based on comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry. The combined untargeted and targeted (UT) fingerprinting strategy covers 452 features, 269 of which were putatively identified and assigned within their characteristic classes. The high amounts of short-chain free fatty acids and alcohols were produced by fermentation and led to a large number of esters. The impact of fermentation was not clearly distinguishable from the control samples; however, had a strong and distinctive signature that was dominated by propionic acid and 1-propanol characteristic volatiles. The approach provides a better understanding of silage stabilization mechanisms against the degradative action of yeasts and molds during the exposure of silage to air.
Topics: 1-Propanol; Aerobiosis; Fatty Acids, Nonesterified; Lactobacillus; Lacticaseibacillus paracasei; Propionates; Silage; Zea mays
PubMed: 36103255
DOI: 10.1021/acs.jafc.2c03652 -
Molecules (Basel, Switzerland) Apr 2023To this day, the quest to find new drugs is still a challenge due to the growing demands of patients suffering from chronic inflammatory diseases and the need for the...
To this day, the quest to find new drugs is still a challenge due to the growing demands of patients suffering from chronic inflammatory diseases and the need for the individualization of therapy. The aim of this research was to synthesize new 1,2,4-triazole derivatives containing propanoic acid moiety and to investigate their anti-inflammatory, antibacterial and anthelmintic activity. Compounds - were obtained in reactions of amidrazones - with succinic anhydride. Several analyses of proton and carbon nuclear magnetic resonance (H NMR, C NMR, respectively), as well as high-resolution mass spectra (HRMS), confirmed the structures of 1,2,4-triazole derivatives -. Toxicity, antiproliferative activity and influence on cytokine release (TNF-α: Tumor Necrosis Factor-α, IL-6: Interleukin-6, IFN-γ: Interferon-γ, and IL-10: Interleukin-10) of the compounds - were evaluated in peripheral blood mononuclear cells culture. Moreover, mitogen-stimulated cell culture was used for biological activity tests. The antimicrobial and anthelmintic activity of derivatives - were studied against Gram-positive and Gram-negative bacterial strains and sp. culture. Despite the lack of toxicity, compounds - significantly reduced the level of TNF-α. Derivatives , and also decreased the release of IFN-γ. Taking all of the results into consideration, compounds , and show the most beneficial anti-inflammatory effects.
Topics: Humans; Propionates; Tumor Necrosis Factor-alpha; Leukocytes, Mononuclear; Anti-Inflammatory Agents; Anti-Infective Agents; Interleukin-6
PubMed: 37175218
DOI: 10.3390/molecules28093808 -
Journal of Dairy Science Mar 1993Sodium carbonates have been fed to ruminants for more than 20 yr and, in many cases, have alleviated milk fat depression. These effects usually have been ascribed to... (Review)
Review
Sodium carbonates have been fed to ruminants for more than 20 yr and, in many cases, have alleviated milk fat depression. These effects usually have been ascribed to increased ruminal buffering capacity, but this mode of action has several problems. For the buffering capacity to increase, the concentrations of ruminal bicarbonate, dissolved CO2, and Na have to increase. Ruminal fluid already is saturated with CO2, and the cation concentration of ruminal fluid is regulated closely to prevent hemoconcentration or hemodilution. Based on these latter observations, a significant increase in ruminal buffering capacity is unlikely. The action of bicarbonates is explained more easily by increased water intake, increased ruminal fluid dilution rate, increased flow of undegraded starch from the rumen, and decreased ruminal propionate production.
Topics: Animals; Carbonates; Cattle; Fermentation; Hydrogen-Ion Concentration; Milk; Propionates; Rumen; Starch
PubMed: 8463492
DOI: 10.3168/jds.S0022-0302(93)77407-X