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The EMBO Journal Feb 2024Metabolic syndrome combines major risk factors for cardiovascular disease, making deeper insight into its pathogenesis important. We here explore the mechanistic basis...
Metabolic syndrome combines major risk factors for cardiovascular disease, making deeper insight into its pathogenesis important. We here explore the mechanistic basis of metabolic syndrome by recruiting an essential patient cohort and performing extensive gene expression profiling. The mitochondrial fatty acid metabolism enzyme acyl-CoA synthetase medium-chain family member 3 (ACSM3) was identified to be significantly lower expressed in the peripheral blood of metabolic syndrome patients. In line, hepatic ACSM3 expression was decreased in mice with metabolic syndrome. Furthermore, Acsm3 knockout mice showed glucose and lipid metabolic abnormalities, and hepatic accumulation of the ACSM3 fatty acid substrate lauric acid. Acsm3 depletion markedly decreased mitochondrial function and stimulated signaling via the p38 MAPK pathway cascade. Consistently, Acsm3 knockout mouse exhibited abnormal mitochondrial morphology, decreased ATP contents, and enhanced ROS levels in their livers. Mechanistically, Acsm3 deficiency, and lauric acid accumulation activated nuclear receptor Hnf4α-p38 MAPK signaling. In line, the p38 inhibitor Adezmapimod effectively rescued the Acsm3 depletion phenotype. Together, these findings show that disease-associated loss of ACSM3 facilitates mitochondrial dysfunction via a lauric acid-HNF4a-p38 MAPK axis, suggesting a novel therapeutic vulnerability in systemic metabolic dysfunction.
Topics: Humans; Mice; Animals; Metabolic Syndrome; p38 Mitogen-Activated Protein Kinases; Liver; Fatty Acids; Coenzyme A Ligases; Lauric Acids
PubMed: 38191811
DOI: 10.1038/s44318-023-00020-1 -
Frontiers in Microbiology 2022In the present study, the inhibitory potential of 14 Trichoderma strains (isolated from Asarum rhizosphere) was investigated against using the plate dilution method....
In the present study, the inhibitory potential of 14 Trichoderma strains (isolated from Asarum rhizosphere) was investigated against using the plate dilution method. The activity of antioxidant enzymes viz; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and malondialdehyde (MDA) in treated with the two Trichoderma strains was also evaluated. Untargeted metabolomic analysis by using LC/MS analysis was carried out to determine differential metabolites in (A26) and (B30) groups. Moreover, transcriptome analysis of during the inhibition of by B30, and A26 compared with the control (CK) was performed. Results indicated that inhibition rates of B30, and A26 were highest compared to other strains. Similarly, non-volatile metabolites extracted from the B30 strain showed a 100% inhibition of . The activity of CAT, SOD, and POD decreased after treatment with A26 and B30 strains while increasing MDA content of . Antifungal activity of differential metabolites like abamectin, eplerenone, behenic acid, lauric acid, josamycin, erythromycin, and minocycline exhibited the highest inhibition of . Transcriptome analysis showed that differentially expressed genes were involved in many metabolic pathways which subsequently contributed toward antifungal activity of Trichoderma. These findings suggested that both Trichoderma strains (B30 and A26) could be effectively used as biocontrol agents against Sclerotinia disease of Asarum.
PubMed: 36267168
DOI: 10.3389/fmicb.2022.997050 -
Physiological Reports Apr 2019Omega-3 fatty acids have long been ascribed a positive cardiovascular function. However, the plasma measurements invariably ignore 40% of the blood specimen, cells that... (Clinical Trial)
Clinical Trial
Omega-3 fatty acids have long been ascribed a positive cardiovascular function. However, the plasma measurements invariably ignore 40% of the blood specimen, cells that engage in continuous exchange with their environment. In our study, we included all components of the circulating blood. Erythrocyte or red-blood-cell (RBC) n-3 fatty acid status has been linked to cardiovascular disease and death. A low omega-3 index is an independent risk factor for cardiovascular disease and mortality. We tested the hypothesis that acute, maximal exercise would influence the relationship between RBC and serum fatty acids. RBC fatty acids profiling was achieved using targeted HPLC-MS mass spectrometry. Healthy volunteers performed maximal treadmill exercise testing using the modified Bruce protocol. Central hemodynamics were monitored and maximal workload was assessed in metabolic equivalents (METs). Venous blood was obtained for RBC lipidomics. With the incremental exercise test, no fatty acid-level variations were found in RBCs, while heart rate and arterial blood pressure increased significantly. No changes occurred in the omega-3 quotient, namely the percentage of eicosapentaenoic acid and docosahexaenoic acid in RBC fatty acids in the RBC membrane. Nonetheless, maximal (13.50 ± 1.97 METs) exercise intensity led to a decrease of RBC lauric acid (C12:0) in the recovery period. These data suggest that despite significant hemodynamic effects, short-term maximal exercise is insufficient to alter RBC n-3 and other fatty-acid status, including the omega-3 quotient, in healthy individuals. RBC lauric acid deserves further scrutiny as a potential regulator of cardiovascular and metabolic functions.
Topics: Adult; Erythrocytes; Exercise; Fatty Acids, Omega-3; Female; Hemodynamics; Humans; Lipidomics; Male; Middle Aged
PubMed: 31016868
DOI: 10.14814/phy2.14040 -
Heliyon Oct 2019Lauric acid (LAH) strongly inhibits the growth of acne-causing bacteria. LAH is essentially water-insoluble and the solubility of laurate (LA) salts are medium and...
Lauric acid (LAH) strongly inhibits the growth of acne-causing bacteria. LAH is essentially water-insoluble and the solubility of laurate (LA) salts are medium and temperature dependent. Hence, LAH/LA preparations are difficult to formulate. Here we fully characterized phospholipid vesicles containing up to 50 mol% LAH. Vesicles of dipalmitoylphosphatidylcholine (DPPC) containing LAH, at pHs 7.4 and 5.0, were characterized measuring size, charge, bilayer phase transition temperature (Tm) and permeability of water-soluble probes. Small angle X-ray scattering and showed multilamellar vesicles at low LAH %. Increasing LAH % had a negligible effect on particle size. An internal aqueous compartment in all vesicle's preparations, even at equimolar DPPC: LAH fractions, was demonstrated using water-soluble probes. At pH 5.0, the interaction between DPPC and LAH increased the Tm and phase transition cooperativity showing a single lipid phase formed by hydrogen-bonded DPPC: LAH complexes. At pH 7.4, vesicles containing 50 mol% LAH exhibited distinct phases, ascribed to complex formation between LAH and LA or LAH and DPPC. LAH incorporated in the vesicles minimally permeated a skin preparation at both pHs, indicating that the primary sites of LAH solubilization were the skin layers. These results provide the foundations for developing processes and products containing DPPC: LAH.
PubMed: 31720452
DOI: 10.1016/j.heliyon.2019.e02648 -
American Journal of Physiology.... Jun 2022Maternal obesity [body mass index (BMI) > 30 kg/m] is associated with greater neonatal adiposity, cord blood (CB) insulin levels, and a proinflammatory phenotype at...
Maternal obesity [body mass index (BMI) > 30 kg/m] is associated with greater neonatal adiposity, cord blood (CB) insulin levels, and a proinflammatory phenotype at birth, contributing to risk of future cardiometabolic disease in the offspring. Variation in neonatal adiposity within maternal BMI groups is underappreciated, and it remains unclear whether the metabolic impairments at birth are an outcome of maternal obesity or excess fetal fat accrual. We examined the hypothesis that CB metabolites associated with fetal fat accrual differ between offspring of normal-weight and obese women. Umbilical venous blood was collected at the time of scheduled cesarean delivery from 50 normal-weight women (LE; pregravid BMI = 22.3 ± 1.7 kg/m) and 50 obese women (OB; BMI = 34.5 ± 3.0 kg/m). Neonatal adiposity was estimated from flank skinfold thickness. The first (low adiposity, LA) and third (high adiposity, HA) tertiles of neonatal %body fat were used to create four groups: OBLA, OBHA, LELA, and LEHA. CB metabolites were measured via untargeted metabolomics. Broadly, the LA offspring of OB women (OBLA) metabolite signature differed from other groups. Lauric acid (C12:0) was 82-118% higher in OBLA vs. all other groups [false discovery rate (FDR) < 0.01]. Several other fatty acids, including palmitate, stearate, and linoleate, were higher in OBLA vs. OBHA groups. CB metabolites, such as lauric acid, a medium-chain fatty acid that may improve insulin sensitivity, were associated with neonatal adiposity differently between offspring of women with and without obesity. Changes in metabolically active lipids at birth may have long-term consequences for offspring metabolism. Using untargeted metabolomics in 100 newborns, we found that cord blood metabolite signatures associated with neonatal adiposity differed between offspring of women with and without obesity.
Topics: Adiposity; Birth Weight; Body Mass Index; Female; Humans; Infant, Newborn; Lauric Acids; Metabolomics; Obesity; Obesity, Maternal; Pregnancy
PubMed: 35466692
DOI: 10.1152/ajpendo.00356.2021 -
Plant Signaling & Behavior Dec 2024Tobacco black shank (TBS), caused by , is a severe disease. Plant root exudates play a crucial role in mediating plant-pathogen interactions in the rhizosphere. However,...
Tobacco black shank (TBS), caused by , is a severe disease. Plant root exudates play a crucial role in mediating plant-pathogen interactions in the rhizosphere. However, the specific interaction between key secondary metabolites present in root exudates and the mechanisms of disease resistance remains poorly understood. This study conducted a comprehensive comparison via quasi-targeted metabolomic analysis on the root exudate metabolites from the tobacco cultivar Yunyan87 and K326, both before and after inoculation with . The results showed that the root exudate metabolites changed after inoculation, and the root exudate metabolites of different tobacco cultivar was significantly different. Furthermore, homovanillic acid, lauric acid, and isoliquiritigenin were identified as potential key compounds for TBS resistance based on their impact on the mycelium growth of the pathogens. The pot experiment showed that isoliquiritigenin reduced the incidence by 55.2%, while lauric acid reduced it by 45.8%. This suggests that isoliquiritigenin and lauric acid have potential applications in the management of TBS. In summary, this study revealed the possible resistance mechanisms of differential metabolites in resistance of commercial tobacco cultivar, and for the first time discovered the inhibitory effects of isoliquiritigenin and homovanillic acid on , and attempt to use plants secondary metabolites of for plant protection.
Topics: Homovanillic Acid; Lauric Acids; Chalcones; Nicotiana
PubMed: 38527068
DOI: 10.1080/15592324.2024.2332019 -
Scientific Reports Jul 2023This work represented the first step toward pioneering the use of a two-stage process for sucrose monolaurate (sucrose ester) production from lauric acid with high...
This work represented the first step toward pioneering the use of a two-stage process for sucrose monolaurate (sucrose ester) production from lauric acid with high productivity and selectivity. In the first stage, lauric acid was firstly converted into methyl laurate via esterification, followed by the transesterification of methyl laurate into sucrose ester in the second stage. In this research, the first stage of process was primarily focused and thoroughly evaluated. Methyl laurate was continuously produced via lauric acid and methanol in a mini fixed-bed reactor. Amberlyst 15 was used as a catalyst. The operating variables were thoroughly investigated and optimized. The optimal condition to achieve 98 wt% yield (99% purity) was as follows: temperature of 110 °C, residence time of 5 min, and feed concentration of 94 g/L. High catalytic stability was observed over the time-on-stream of 30 h. This process provided good productivity compared to the other processes. The methyl laurate obtained from the first stage could be used as a raw material for the second stage to produce sucrose ester, which was demonstrated experimentally. The high selectivity of 95% of sucrose monolaurate was obtained. The continuous production of sucrose ester from lauric acid could be achieved.
PubMed: 37433839
DOI: 10.1038/s41598-023-38461-7 -
RSC Advances Apr 2022Molybdenum oxide-modified ruthenium on titanium oxide (Ru-()MoO /TiO; is the loading amount of Mo) catalysts show high activity for the hydroconversion of carboxylic...
Molybdenum oxide-modified ruthenium on titanium oxide (Ru-()MoO /TiO; is the loading amount of Mo) catalysts show high activity for the hydroconversion of carboxylic acids to the corresponding alcohols (fatty alcohols) and aliphatic alkanes (biofuels) in 2-propanol/water (4.0/1.0 v/v) solvent in a batch reactor under mild reaction conditions. Among the Ru-()MoO /TiO catalysts tested, the Ru-(0.026)MoO /TiO (Mo loading amount of 0.026 mmol g) catalyst shows the highest yield of aliphatic -alkanes from hydroconversion of coconut oil derived lauric acid and various aliphatic fatty acid C6-C18 precursors at 170-230 °C, 30-40 bar for 7-20 h. Over Ru-(0.026)MoO /TiO, as the best catalyst, the hydroconversion of lauric acid at lower reaction temperatures (130 ≥ ≤ 150 °C) produced dodecane-1-ol and dodecyl dodecanoate as the result of further esterification of lauric acid and the corresponding alcohols. An increase in reaction temperature up to 230 °C significantly enhanced the degree of hydrodeoxygenation of lauric acid and produced -dodecane with maximum yield (up to 80%) at 230 °C, H 40 bar for 7 h. Notably, the reusability of the Ru-(0.026)MoO /TiO catalyst is slightly limited by the aggregation of Ru nanoparticles and the collapse of the catalyst structure.
PubMed: 35520112
DOI: 10.1039/d2ra02103j -
Animals : An Open Access Journal From... Feb 2023This experiment investigated the benefits of plant essential oil (EO) composed with lauric acid monoglyceride and cinnamaldehyde on necrotic enteritis-challenged...
Complex of Lauric Acid Monoglyceride and Cinnamaldehyde Ameliorated Subclinical Necrotic Enteritis in Yellow-Feathered Broilers by Regulating Gut Morphology, Barrier, Inflammation and Serum Biochemistry.
This experiment investigated the benefits of plant essential oil (EO) composed with lauric acid monoglyceride and cinnamaldehyde on necrotic enteritis-challenged broilers. A total of 180 1-day-old healthy yellow-feathered broilers were randomly divided into 4 groups with 3 replicates of 15 chicks each. The experimental groups were as follows: the control group (CON) was fed with the basal diet and was not challenged by (EA) and (CP); CPEA group was also fed with a basal diet, but infected with CP and EA; CPEA_EO350 group and CPEA_EO500 group were fed with a basal diet supplemented with 350 and 500 mg/kg EO, respectively, and all infected with CP and EA. On the 7th day, each bird in the CPEA group, CPEA_EO350 group and CPEA_EO500 group was orally administrated with 1 mL containing 5000 oocytes/mL, and the birds of the CON group were orally administrated with 1 mL normal saline. From the 15th day, 1 mL of CP type A CVCC-2030 strain (about 5 × 10 cfu/mL) was orally inoculated into each bird of the CPEA, CPEA_EO350 and CPEA_EO500 groups for three consecutive days. Similarly, the CON group was orally given 1 mL of normal saline. The CPEA stimulation reduced the average daily gain (ADG) of broilers, increased the feed-to-gain ratio (F:G), and increased the intestinal lesions of the broilers ( < 0.01), indicating that CPEA stimulation was clinically successful. Compared with the CPEA group, the ADG of CPEA_EO350 and CPEA_EO500 increased, the F:G decreased ( < 0.01), and the intestinal score of CPEA_EO500 decreased ( < 0.01). The expression of the tight junction protein of the jejunum and ileum on 21d was upregulated ( < 0.01), and the expression of jejunum inflammation factors TNF-α on 21d and jejunum and ileum inflammatory factor IL-6 on 28d were also downregulated. The CPEA_EO350 and CPEA_EO500 increased antioxidant capacity. To sum up, 350 and 500 mg/kg of lauric acid monoglyceride and cinnamaldehyde complex plant essential oils can improve ADG and F:G, improve intestinal morphology and the body's antioxidant capacity, and downregulate the expression of inflammatory factors. The concentration of 500 mg/kg performed even better.
PubMed: 36766404
DOI: 10.3390/ani13030516 -
Nutrients Dec 2022Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where...
Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where they are immediately utilized for energy. We aimed to determine the medium-chain fatty acid levels in women with and without breast cancer. A total of 200 women (100 breast cancer subjects and 100 control subjects) were recruited for the study as per the inclusion and exclusion criteria. Blood samples were collected for biochemical estimations. Fatty acid methyl esters were isolated, and medium-chain fatty acid levels in plasma were analyzed using gas chromatography (GC-FID). Statistical analysis was performed using SPSS 20.0 software; ≤ 0.05 was considered statistically significant. The fatty acid analysis revealed a significant decrease in the levels of caprylic acid (C:8) and lauric acid (C:12) and a significant increase in the level of capric acid (C:10) in the breast cancer subjects when compared to the control group. The level of caproic acid (C:6) was not significantly increased in the breast cancer subjects. In particular, the HER2- and ER-positive breast cancer subjects showed a decrease in their caprylic acid and lauric acid levels compared to other receptors. The results of the current study imply that lower levels of caprylic and lauric acid may be associated with a higher risk of breast cancer. The relevance of medium-chain fatty acids for preventive and therapeutic interventions will be amplified by further research on the possibility that alteration in a patient's medium-chain fatty acid composition may mechanistically contribute to disease progression or breast cancer risk.
Topics: Humans; Female; Caprylates; Breast Neoplasms; Fatty Acids; Lauric Acids
PubMed: 36558514
DOI: 10.3390/nu14245351