This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and ...This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.展开更多
Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer mem...Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.展开更多
Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpos...Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpose of our study was to comprehensively evaluate its effects on the growth performance based on the average daily gain(ADG), average daily feed intake(ADFI) and gain: feed(G:F) ratio and to unveil the roles of the basal diet, LCFA concentration and LCFA saturation.Results: We searched the Pub Med and Web of Science databases(articles published from Jan 1 st, 2000, to Sep 30 th,2018;restricted to English) and compared LCFA-supplemented diets with control diets. We retrieved 2346 studies, 18 of which(1314 pigs, 26 records) were eligible for our analysis. We used a random-effects model to calculate the weighted mean differences(WMDs) and 95% confidence intervals(CIs). LCFA supplementation in the grower-finisher phase improved the ADG(WMD = 41.74 g/d, 95% CI: 8.81 to 74.66, P = 0.013) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P = 0.003). For supplementation solely in the finisher phase, we found a similar performance in the ADG(WMD = 39.93 g/d, 95% CI: 26.48 to 53.38, P < 0.001) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P < 0.001) but a reduction in the ADFI(WMD =-83.863 g/d, 95% CI:-156.157 to-11.569, P = 0.023). Specifically, approximately 5%LCFA supplementation in the finisher phase had significant effects on the ADG(WMD = 51.385 g/d, 95% CI: 35.816 to66.954, P < 0.001), ADFI(WMD =-102.869 g/d, 95% CI:-189.236 to-16.502, P = 0.02) and G:F ratio(WMD = 0.028, 95%CI: 0.018 to 0.039, P < 0.001), whereas a concentration of approximately 1% exhibited no effects.Conclusions: Overall, regardless of the basal diet and saturation, LCFA supplementation greatly improves the growth performance of grower and finisher pigs, primarily by increasing the energy density.展开更多
This study investigated the effects of the degree of unsaturation(unsaturity) of long-chain fatty acids on microbial protein content and the activities of transaminases and dehydrogenase in vitro using goat rumen fl...This study investigated the effects of the degree of unsaturation(unsaturity) of long-chain fatty acids on microbial protein content and the activities of transaminases and dehydrogenase in vitro using goat rumen fluid as the cultural medium.Six types of fatty acids,stearic acid(C18:0,group A,control group),oleic acid(C18:1,n-9,group B),linoleic acid(C18:2,n-6,group C),α-linolenic acid(C18:3,n-3,group D),arachidonic acid(C20:4,n-6,group E),and eicosapentaenoic acid(C20:5,n-3,group F),were tested,and the inclusion ratio of each fatty acid was 3%(w/w) in total of culture substrate.Samples were taken at 0,3,6,9,12,18 and 24 h,respectively,during culture for analyses.Compared with stearic acid,linoleic acid,a-linolenic acid,and arachidonic acid increased the bacterial protein content,while oleic acid and eicosapentaenoic acid had no significant effects;the protozoal protein content was reduced for all the unsaturated fatty acids,and the magnitude of the reduction appeared to be associated with the degree of unsaturity of fatty acids.The total microbial protein content was dominantly accounted by the protozoal protein content(about 4-9 folds of the bacterial protein),and only increased by linoleic acid,but reduced by oleic acid,arachidonic acid and eicosapentaenoic acid.There were no significant effects in the activities of both glutamic oxaloacetic transaminase(GOT) and glutamic-pyruvic transaminase(GPT) for all the other fatty acids,except for arachidonic acid which enhanced GOT activity and oleic acid which enhanced GPT activity.The total dehydrogenase activity was positively correlated with the degree of unsaturation of fatty acids.In conclusion,the inclusion of 3%of long-chain unsaturated fatty acids increased bacterial protein content,whereas reduced protozoal protein content and enhanced dehydrogenase activity.The fatty acids with more than three double bonds had detrimental effects on the microbial protein content.This work demonstrates for the first time the effect rule of the unsaturation degree of long-chain fatty acids on the rumen microbial protein in vitro.展开更多
This article reviewed the inhibition mechanism of long chain fatty acid on the formation of anaerobic system, then thoroughly analyzed the inhibition factors of long chain fatty acid, and summarized the remission meth...This article reviewed the inhibition mechanism of long chain fatty acid on the formation of anaerobic system, then thoroughly analyzed the inhibition factors of long chain fatty acid, and summarized the remission method to its inhibition, finally proposed some suggestions to further study on the influence of long chain fatty acid on anaerobic digestion system.展开更多
Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(MCFA)as in-feed additives.This stu...Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(MCFA)as in-feed additives.This study evaluated the potential of a novel blend of MCFA salts(DIC)from distilled coconut oil with a lauric acid content to reduce enteropathogens and control intestinal diseases around weaning.Two experimental disease models were implemented in early-weaned piglets,consisting of two oral challenges:Salmonella Typhimurium(1.2×10~8 CFU)or enterotoxigenic Escherichia coli(ETEC)F4(1.5×10~9 CFU).The parameters assessed were:animal performance,clinical signs,pathogen excretion,intestinal fermentation,immune-inflammatory response,and intestinal morphology.Results:The Salmonella challenge promoted an acute course of diarrhea,with most of the parameters responding to the challenge,whereas the ETEC F4 challenge promoted a mild clinical course.A consistent antipathogenic effect of DIC was observed in both trials in the hindgut,with reductions in Salmonella spp.plate counts in the cecum(P=0.03)on d 8 post-inoculation(PI)(Salmonella trial),and of enterobacteria and total coliform counts in the ileum and colon(P<0.10)on d 8 PI(ETEC F4 trial).When analyzing the entire colonic microbiota(16 S rRNA gene sequencing),this additive tended(P=0.13)to reduce the Firmicutes/Bacteroidetes ratio and enriched Fibrobacteres after the Salmonella challenge.In the ETEC F4 challenge,DIC prompted structural changes in the ecosystem with increases in Dialister,and a trend(P=0.14)to increase the Veillonellaceae family.Other parameters such as the intestinal fermentation products or serum pro-inflammatory mediators were not modified by DIC supplementation,nor were the histological parameters.Only the intraepithelial lymphocyte(IEL)counts were lowered by DIC in animals challenged with Salmonella(P=0.07).With ETEC F4,the IEL counts were higher with DIC on d 8 PI(P=0.08).Conclusions:This study confirms the potential activity of this MCFA salts mixture to reduce intestinal colonization by opportunistic pathogens such as Salmonella or E.coli and its ability to modulate colonic microbiota.These changes could explain to some extent the local immune cell response at the ileal level.展开更多
This study investigated the impacts of the degree of unsaturation (unsaturity) of long-chain fatty acids on volatile fatty acid (VFA) profiles of rumen fermentation in vitro. Six types of long-chain fatty acids, i...This study investigated the impacts of the degree of unsaturation (unsaturity) of long-chain fatty acids on volatile fatty acid (VFA) profiles of rumen fermentation in vitro. Six types of long-chain fatty acids, including stearic acid (C18:0, control group), oleic acid (C18:1, n-9), linoleic acid (C18:2, n-6), a-linolenic acid (C18:3, n-3), arachidonic acid (C20:4, n-6) and eicosapentaenoic acid (C20:5, n-3), were tested. Rumen fluid from three goats fitted with ruminal fistulae was used as inoculum and the inclusion rate of long-chain fatty acid was at 3% (w/w) of substrate. Samples were taken for VFA analysis at 0, 3, 6, 9, 12, 18 and 24 h of incubation, respectively. The analysis showed that there were significant differences in the total VFA among treatments, sampling time points, and treatment×time point interactions (P〈0.01). a-Linolenic acid had the highest total VFA (P〈0.01) among different long-chain fatty acids tested. The molar proportion of acetate in total VFA significantly differed among treatments (P〈0.01) and sampling time points (P〈0.01), but not treatment×time point interactions (P〉0.05). In contrast, the molar proportion of propionate did not differ among treatments during the whole incubation (P〉0.05). However, for butyrate molar proportions, significant differences were found not only among sampling time points but also among treatments and treatment×time point interactions (P〈0.01), with eicosapentaenoic acid having the highest value (P〈0.01). Additionally, no statistically significant differences were found in the acetate to propionate ratios among treatments groups (P〉0.05), even the treatments stearic acid and a-linolenic acid were numerically higher than the others. The inclusion of 3% long-chain unsaturated fatty acids differing in the degree of unsaturation brought out a significant quadratic regression relation between the total VFA concentration and the double bond number of fatty acid. In conclusion, the a-linolenic acid with 3 double bonds appeared better for improving rumen microbial fermentation and the total VFA concentration.展开更多
The marine microalga Nannochloropsis sp.contains various elongases and desaturases that are critical for biosynthesis of polyunsaturated fatty acids.A full-length cDNA encoding a long-chain fatty acid elongase,named N...The marine microalga Nannochloropsis sp.contains various elongases and desaturases that are critical for biosynthesis of polyunsaturated fatty acids.A full-length cDNA encoding a long-chain fatty acid elongase,named Ns FAE,was cloned from Nannochloropsis sp..The open reading frame of Ns FAE(GenBank accession no.MF680548)consisted of 1068 bp and encoded a predicted protein of 355 amino acids with molecular mass 38.8 k Da.The deduced polypeptide showed 43%–44%identity to fatty acyl elongases from other algae.RT-PCR experiments indicated that the Ns FAE gene exhibited the highest expression in Nannochloropsis sp.at 72 h(i.e.,during the third growth stage)and the expression was significantly lower in the other four growth stages.Plasmid p Ns FAE-CRISPR and a recombinant DNA fragment(ADH1p-Ns FAE-CYCt)were transformed into Saccharomyces cerevisiae strain BY4742 using the CRISPR-Cas system.Yeast transformants containing Ns FAE produced three fatty acids not normally present in wild-type BY4742-linoleic acid,linolenic acid and eicosadienoic acid-indicating that Ns FAE encodes a functional elongase enzyme.展开更多
Resting cells of Nocardia sp.were used to convert a series of unsaturated long-chain fatty acids to 10-hvdroxy fatty acids.Structures of all metabolites were suggested by 1Hnuclear magnetic resonance and mass spectrum...Resting cells of Nocardia sp.were used to convert a series of unsaturated long-chain fatty acids to 10-hvdroxy fatty acids.Structures of all metabolites were suggested by 1Hnuclear magnetic resonance and mass spectrum.The results showed that the hydroxylation sterospecificity happened at the cis-9 double bond with other position unaffected.展开更多
Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate...Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate usefulness of Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection (ATR) analysis method for clinical diagnosis of those diseases, thereby we measured the infrared spectra of the sera of patients and healthy controls. Correlation coefficients between 2nd derivative FTIR spectra of the serum samples and the VLCFA content ratio which is used as a clinical parameter to date were comprehensively calculated to investigate which wavenumber showed high correlation with the VLCFA ratio. Multiple regression analysis using the serum FTIR spectra showed that high correlations were observed with VLCFA ratios (C26:0/C22:0 ratio), and we could construct a suitable regression model (R2 = 0.97, p ﹣19). In addition, the model system using various VLCFAs in newborn bovine serum also showed that several FTIR peaks in 800 ~ 900 cm﹣1 region were found to have good correlation with VLCFA ratios. Our results support that FTIR analysis is useful for diagnosis of peroxisomal diseases.展开更多
Diabetes mellitus or hypoinsulinemia was induced successfully in the male dwarf goats aged be-tween 2 - 3 years with 2 consecutive administrations of streptozotocin. A comparable group of intact control goats was also...Diabetes mellitus or hypoinsulinemia was induced successfully in the male dwarf goats aged be-tween 2 - 3 years with 2 consecutive administrations of streptozotocin. A comparable group of intact control goats was also maintained. In ruminants including goats unlike non-ruminants, insulin generally displays ineffectiveness or resistance in their biochemical setup to facilitate gluco-neogenesis, the only source of glucose in these animals. In present study almost in the absence of insulin through induced hypoinsulinemia the effects of thyrotropin releasing hormone (TRH) (30 μg/kg body weight) and thyroid stimulating hormone (TSH) (2.5 μg/kg body weight) on circulatory glucose and different fatty acid fractions were studied in insulin resistant ruminant model. Fatty acid fractions were estimated by gas chromatography. Both TRH and TSH administration lowered glycemia in insulin deficient goats compared to the controls but significantly with TSH dose only. In intact goats the detectable circulating long chain fatty acids (LCFAs) fractions of lauric, myristic, palmitic, stearic, oleic and linoleic acid were undetected except linoleic acid in the hypoinsulinemic state, however were found restored following TRH and TSH administrations and some of LCFAs;stearic (6417%), oleic (1676%) and linoleic acid (1225%) increased exceptionally with TSH dose. In Intact goats however the hormones variedly increased the fractions. The volatile fatty acid fractions (VFAs) of formic, acetic, propionic, iso-butyric, n-butyric, iso-valeric, n-valeric, iso-caproic, n-caproic and heptanoic acid were detected in the goats. The most VFAs fractions markedly increased in hypoinsulinemic goats compared to the control goats following TRH and TSH infusion. These results have indicated that endogenously stimulated thyroid hormones with TRH and TSH in insulin deficient state inhibit the mechanisms of utilizing the fatty acids in glucose production. Therefore the study reveals thyroid hormones inhibitory effects on gluconeogenesis in insulin resistance and hyperglycemia.展开更多
Amyloid peptide, the main component of senile plaques, is a major biological characteristic of Alzheimer’s disease (AD). The aim of the present study conducted on human neuronal SK-N-BE cells was to evaluate whether ...Amyloid peptide, the main component of senile plaques, is a major biological characteristic of Alzheimer’s disease (AD). The aim of the present study conducted on human neuronal SK-N-BE cells was to evaluate whether oligomerized Aβ1-40-induced cell damages was associated with lipid modifications. Under treatment with Aβ1-40 (10 - 100 μM;24 - 48 h), cell viability was recorded with the MTT test and by measuring LDH activity. Mitochondrial transmembrane potential and ATP production were assessed using flow cytometry and a luciferase-based ATP bioluminescence assay, respectively. Annexin V-CF647 staining assay for cell apoptosis detection was performed using flow cytometry. Potentially intracellular cytotoxic lipids (oxysterols: 7α-hydroxycholesterol (7α-OHC), 7β-hydroxycholesterol (7β-OHC), and 7-ketocholesterol (7KC), 24(S)-hydroxycholesterol;arachidonic acid (C20:4 n-6);VLCFAs (C22:0, C24:0, C24:6 and C26:0)) were measured using gas chromatography coupled with mass spectrometry. The cellular level of docosahexaenoic acid (C22:6 n-3), often altered in AD, was also quantified. In the presence of Aβ1-40, the percentage of MTT-positive cells decreased and was associated with an increase in LDH activity. In addition, treatment with oligomerized Aβ1-40 induced a decrease of mitochondrial transmembrane potential as well as an apoptotic cell death. Sterol analysis revealed a higher cholesterol level and a significant increase of cytotoxic oxysterols per cell (7KC + 7β-OHC), and of the [(7β-OHC + 7KC)/cholesterol] ratio, considered as a lipid peroxidation index, in Aβ1-40-treated cells. An enhancement of C20:4 n-6, C22:6 n-3 and saturated VLCFAs was also observed. Therefore, Aβ1-40-induced side effects are associated with intracellular accumulation of lipids, especially cholesterol, oxysterols (7β-OHC, 7KC), C20:4 n-6, and saturated VLCFAs, which could in turn contribute to neurotoxicity.展开更多
Fatty acids with different chain length were deoxygenated in the absence of hydrogen (caprylic acid (CA), lauric acid (LA) and stearic acid (SA)). The catalytic tests were carried over Pd-containing catalysts out in a...Fatty acids with different chain length were deoxygenated in the absence of hydrogen (caprylic acid (CA), lauric acid (LA) and stearic acid (SA)). The catalytic tests were carried over Pd-containing catalysts out in a batch reactor under inert gas for 6 h at 250°C to 350°C and pressures from 18 to 75 bar in the absence of additionally fed hydrogen. Pd-containing catalysts were tested;the best performing catalyst was 10% Pd/C with 63% undecane yield at 327°C. These catalysts were used for a comparative decarboxylation of CA, LA and SA. At equal reaction conditions (300°C, 6 h), the chain length of the fatty acid had a strong impact on the conversion, which was steadily increasing, whereas the alkane selectivity ran through a maximum. This work demonstrated the usability of Pd-containing catalysts for the decarboxylation of various fatty acids in the absence of additionally fed hydrogen with respect to the manufacture of hydrocarbons that can be used as blending components for fuels.展开更多
To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofi...To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.展开更多
基金the National Natural Science Foundation of China(Grant Nos.82072816 and 81672553)the Natural Science Foundation of Shandong Province(Grant No.ZR2021LZY003).
文摘This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.
基金Supported by National Natural Science Foundation of China,No.81373465
文摘Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.
基金supported by the Key Program of the National Natural Science Foundation of China(grant#3163000269)National Special Fund for Modern Industrial Technology System(grant#CARS-35)Major Science and Technology Special Fund of Zhejiang Province(grant#2015C02022)
文摘Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpose of our study was to comprehensively evaluate its effects on the growth performance based on the average daily gain(ADG), average daily feed intake(ADFI) and gain: feed(G:F) ratio and to unveil the roles of the basal diet, LCFA concentration and LCFA saturation.Results: We searched the Pub Med and Web of Science databases(articles published from Jan 1 st, 2000, to Sep 30 th,2018;restricted to English) and compared LCFA-supplemented diets with control diets. We retrieved 2346 studies, 18 of which(1314 pigs, 26 records) were eligible for our analysis. We used a random-effects model to calculate the weighted mean differences(WMDs) and 95% confidence intervals(CIs). LCFA supplementation in the grower-finisher phase improved the ADG(WMD = 41.74 g/d, 95% CI: 8.81 to 74.66, P = 0.013) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P = 0.003). For supplementation solely in the finisher phase, we found a similar performance in the ADG(WMD = 39.93 g/d, 95% CI: 26.48 to 53.38, P < 0.001) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P < 0.001) but a reduction in the ADFI(WMD =-83.863 g/d, 95% CI:-156.157 to-11.569, P = 0.023). Specifically, approximately 5%LCFA supplementation in the finisher phase had significant effects on the ADG(WMD = 51.385 g/d, 95% CI: 35.816 to66.954, P < 0.001), ADFI(WMD =-102.869 g/d, 95% CI:-189.236 to-16.502, P = 0.02) and G:F ratio(WMD = 0.028, 95%CI: 0.018 to 0.039, P < 0.001), whereas a concentration of approximately 1% exhibited no effects.Conclusions: Overall, regardless of the basal diet and saturation, LCFA supplementation greatly improves the growth performance of grower and finisher pigs, primarily by increasing the energy density.
基金financially supported by the Innovation Foundation for Undergraduate of Yangzhou University,China (201311117034)the Domestic Cooperative Innovation ofIndustry-University-Research(XT20140012)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China
文摘This study investigated the effects of the degree of unsaturation(unsaturity) of long-chain fatty acids on microbial protein content and the activities of transaminases and dehydrogenase in vitro using goat rumen fluid as the cultural medium.Six types of fatty acids,stearic acid(C18:0,group A,control group),oleic acid(C18:1,n-9,group B),linoleic acid(C18:2,n-6,group C),α-linolenic acid(C18:3,n-3,group D),arachidonic acid(C20:4,n-6,group E),and eicosapentaenoic acid(C20:5,n-3,group F),were tested,and the inclusion ratio of each fatty acid was 3%(w/w) in total of culture substrate.Samples were taken at 0,3,6,9,12,18 and 24 h,respectively,during culture for analyses.Compared with stearic acid,linoleic acid,a-linolenic acid,and arachidonic acid increased the bacterial protein content,while oleic acid and eicosapentaenoic acid had no significant effects;the protozoal protein content was reduced for all the unsaturated fatty acids,and the magnitude of the reduction appeared to be associated with the degree of unsaturity of fatty acids.The total microbial protein content was dominantly accounted by the protozoal protein content(about 4-9 folds of the bacterial protein),and only increased by linoleic acid,but reduced by oleic acid,arachidonic acid and eicosapentaenoic acid.There were no significant effects in the activities of both glutamic oxaloacetic transaminase(GOT) and glutamic-pyruvic transaminase(GPT) for all the other fatty acids,except for arachidonic acid which enhanced GOT activity and oleic acid which enhanced GPT activity.The total dehydrogenase activity was positively correlated with the degree of unsaturation of fatty acids.In conclusion,the inclusion of 3%of long-chain unsaturated fatty acids increased bacterial protein content,whereas reduced protozoal protein content and enhanced dehydrogenase activity.The fatty acids with more than three double bonds had detrimental effects on the microbial protein content.This work demonstrates for the first time the effect rule of the unsaturation degree of long-chain fatty acids on the rumen microbial protein in vitro.
文摘This article reviewed the inhibition mechanism of long chain fatty acid on the formation of anaerobic system, then thoroughly analyzed the inhibition factors of long chain fatty acid, and summarized the remission method to its inhibition, finally proposed some suggestions to further study on the influence of long chain fatty acid on anaerobic digestion system.
基金funded by the“PORCDIGEST”project(IDI-20140262)funded by the CDTI and the Ministerio de Economía y Competitividad(Spain)support from the pre-doctoral FI grant of the Generalitat de Catalunya(Spain)awarded to Paola López-Colom.
文摘Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(MCFA)as in-feed additives.This study evaluated the potential of a novel blend of MCFA salts(DIC)from distilled coconut oil with a lauric acid content to reduce enteropathogens and control intestinal diseases around weaning.Two experimental disease models were implemented in early-weaned piglets,consisting of two oral challenges:Salmonella Typhimurium(1.2×10~8 CFU)or enterotoxigenic Escherichia coli(ETEC)F4(1.5×10~9 CFU).The parameters assessed were:animal performance,clinical signs,pathogen excretion,intestinal fermentation,immune-inflammatory response,and intestinal morphology.Results:The Salmonella challenge promoted an acute course of diarrhea,with most of the parameters responding to the challenge,whereas the ETEC F4 challenge promoted a mild clinical course.A consistent antipathogenic effect of DIC was observed in both trials in the hindgut,with reductions in Salmonella spp.plate counts in the cecum(P=0.03)on d 8 post-inoculation(PI)(Salmonella trial),and of enterobacteria and total coliform counts in the ileum and colon(P<0.10)on d 8 PI(ETEC F4 trial).When analyzing the entire colonic microbiota(16 S rRNA gene sequencing),this additive tended(P=0.13)to reduce the Firmicutes/Bacteroidetes ratio and enriched Fibrobacteres after the Salmonella challenge.In the ETEC F4 challenge,DIC prompted structural changes in the ecosystem with increases in Dialister,and a trend(P=0.14)to increase the Veillonellaceae family.Other parameters such as the intestinal fermentation products or serum pro-inflammatory mediators were not modified by DIC supplementation,nor were the histological parameters.Only the intraepithelial lymphocyte(IEL)counts were lowered by DIC in animals challenged with Salmonella(P=0.07).With ETEC F4,the IEL counts were higher with DIC on d 8 PI(P=0.08).Conclusions:This study confirms the potential activity of this MCFA salts mixture to reduce intestinal colonization by opportunistic pathogens such as Salmonella or E.coli and its ability to modulate colonic microbiota.These changes could explain to some extent the local immune cell response at the ileal level.
基金financially supported by the Graduate Student Innovation Project of Jiangsu Province,China (KYLX15_1377)the Natural Science Foundation of Jiangsu Province,China (BK20151312)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD),China
文摘This study investigated the impacts of the degree of unsaturation (unsaturity) of long-chain fatty acids on volatile fatty acid (VFA) profiles of rumen fermentation in vitro. Six types of long-chain fatty acids, including stearic acid (C18:0, control group), oleic acid (C18:1, n-9), linoleic acid (C18:2, n-6), a-linolenic acid (C18:3, n-3), arachidonic acid (C20:4, n-6) and eicosapentaenoic acid (C20:5, n-3), were tested. Rumen fluid from three goats fitted with ruminal fistulae was used as inoculum and the inclusion rate of long-chain fatty acid was at 3% (w/w) of substrate. Samples were taken for VFA analysis at 0, 3, 6, 9, 12, 18 and 24 h of incubation, respectively. The analysis showed that there were significant differences in the total VFA among treatments, sampling time points, and treatment×time point interactions (P〈0.01). a-Linolenic acid had the highest total VFA (P〈0.01) among different long-chain fatty acids tested. The molar proportion of acetate in total VFA significantly differed among treatments (P〈0.01) and sampling time points (P〈0.01), but not treatment×time point interactions (P〉0.05). In contrast, the molar proportion of propionate did not differ among treatments during the whole incubation (P〉0.05). However, for butyrate molar proportions, significant differences were found not only among sampling time points but also among treatments and treatment×time point interactions (P〈0.01), with eicosapentaenoic acid having the highest value (P〈0.01). Additionally, no statistically significant differences were found in the acetate to propionate ratios among treatments groups (P〉0.05), even the treatments stearic acid and a-linolenic acid were numerically higher than the others. The inclusion of 3% long-chain unsaturated fatty acids differing in the degree of unsaturation brought out a significant quadratic regression relation between the total VFA concentration and the double bond number of fatty acid. In conclusion, the a-linolenic acid with 3 double bonds appeared better for improving rumen microbial fermentation and the total VFA concentration.
基金supported by the Basic Scientific Fund for National Public Research Institutes of China (No. 2016Q07)
文摘The marine microalga Nannochloropsis sp.contains various elongases and desaturases that are critical for biosynthesis of polyunsaturated fatty acids.A full-length cDNA encoding a long-chain fatty acid elongase,named Ns FAE,was cloned from Nannochloropsis sp..The open reading frame of Ns FAE(GenBank accession no.MF680548)consisted of 1068 bp and encoded a predicted protein of 355 amino acids with molecular mass 38.8 k Da.The deduced polypeptide showed 43%–44%identity to fatty acyl elongases from other algae.RT-PCR experiments indicated that the Ns FAE gene exhibited the highest expression in Nannochloropsis sp.at 72 h(i.e.,during the third growth stage)and the expression was significantly lower in the other four growth stages.Plasmid p Ns FAE-CRISPR and a recombinant DNA fragment(ADH1p-Ns FAE-CYCt)were transformed into Saccharomyces cerevisiae strain BY4742 using the CRISPR-Cas system.Yeast transformants containing Ns FAE produced three fatty acids not normally present in wild-type BY4742-linoleic acid,linolenic acid and eicosadienoic acid-indicating that Ns FAE encodes a functional elongase enzyme.
文摘Resting cells of Nocardia sp.were used to convert a series of unsaturated long-chain fatty acids to 10-hvdroxy fatty acids.Structures of all metabolites were suggested by 1Hnuclear magnetic resonance and mass spectrum.The results showed that the hydroxylation sterospecificity happened at the cis-9 double bond with other position unaffected.
文摘Very long chain fatty acids (VLCFAs) are accumulated in cells and blood in patients with peroxisomal diseases, such as adrenoleukodystrophy (ALD) and Zellwger Syndrome (ZS). The purpose of this study is to investigate usefulness of Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection (ATR) analysis method for clinical diagnosis of those diseases, thereby we measured the infrared spectra of the sera of patients and healthy controls. Correlation coefficients between 2nd derivative FTIR spectra of the serum samples and the VLCFA content ratio which is used as a clinical parameter to date were comprehensively calculated to investigate which wavenumber showed high correlation with the VLCFA ratio. Multiple regression analysis using the serum FTIR spectra showed that high correlations were observed with VLCFA ratios (C26:0/C22:0 ratio), and we could construct a suitable regression model (R2 = 0.97, p ﹣19). In addition, the model system using various VLCFAs in newborn bovine serum also showed that several FTIR peaks in 800 ~ 900 cm﹣1 region were found to have good correlation with VLCFA ratios. Our results support that FTIR analysis is useful for diagnosis of peroxisomal diseases.
文摘Diabetes mellitus or hypoinsulinemia was induced successfully in the male dwarf goats aged be-tween 2 - 3 years with 2 consecutive administrations of streptozotocin. A comparable group of intact control goats was also maintained. In ruminants including goats unlike non-ruminants, insulin generally displays ineffectiveness or resistance in their biochemical setup to facilitate gluco-neogenesis, the only source of glucose in these animals. In present study almost in the absence of insulin through induced hypoinsulinemia the effects of thyrotropin releasing hormone (TRH) (30 μg/kg body weight) and thyroid stimulating hormone (TSH) (2.5 μg/kg body weight) on circulatory glucose and different fatty acid fractions were studied in insulin resistant ruminant model. Fatty acid fractions were estimated by gas chromatography. Both TRH and TSH administration lowered glycemia in insulin deficient goats compared to the controls but significantly with TSH dose only. In intact goats the detectable circulating long chain fatty acids (LCFAs) fractions of lauric, myristic, palmitic, stearic, oleic and linoleic acid were undetected except linoleic acid in the hypoinsulinemic state, however were found restored following TRH and TSH administrations and some of LCFAs;stearic (6417%), oleic (1676%) and linoleic acid (1225%) increased exceptionally with TSH dose. In Intact goats however the hormones variedly increased the fractions. The volatile fatty acid fractions (VFAs) of formic, acetic, propionic, iso-butyric, n-butyric, iso-valeric, n-valeric, iso-caproic, n-caproic and heptanoic acid were detected in the goats. The most VFAs fractions markedly increased in hypoinsulinemic goats compared to the control goats following TRH and TSH infusion. These results have indicated that endogenously stimulated thyroid hormones with TRH and TSH in insulin deficient state inhibit the mechanisms of utilizing the fatty acids in glucose production. Therefore the study reveals thyroid hormones inhibitory effects on gluconeogenesis in insulin resistance and hyperglycemia.
文摘Amyloid peptide, the main component of senile plaques, is a major biological characteristic of Alzheimer’s disease (AD). The aim of the present study conducted on human neuronal SK-N-BE cells was to evaluate whether oligomerized Aβ1-40-induced cell damages was associated with lipid modifications. Under treatment with Aβ1-40 (10 - 100 μM;24 - 48 h), cell viability was recorded with the MTT test and by measuring LDH activity. Mitochondrial transmembrane potential and ATP production were assessed using flow cytometry and a luciferase-based ATP bioluminescence assay, respectively. Annexin V-CF647 staining assay for cell apoptosis detection was performed using flow cytometry. Potentially intracellular cytotoxic lipids (oxysterols: 7α-hydroxycholesterol (7α-OHC), 7β-hydroxycholesterol (7β-OHC), and 7-ketocholesterol (7KC), 24(S)-hydroxycholesterol;arachidonic acid (C20:4 n-6);VLCFAs (C22:0, C24:0, C24:6 and C26:0)) were measured using gas chromatography coupled with mass spectrometry. The cellular level of docosahexaenoic acid (C22:6 n-3), often altered in AD, was also quantified. In the presence of Aβ1-40, the percentage of MTT-positive cells decreased and was associated with an increase in LDH activity. In addition, treatment with oligomerized Aβ1-40 induced a decrease of mitochondrial transmembrane potential as well as an apoptotic cell death. Sterol analysis revealed a higher cholesterol level and a significant increase of cytotoxic oxysterols per cell (7KC + 7β-OHC), and of the [(7β-OHC + 7KC)/cholesterol] ratio, considered as a lipid peroxidation index, in Aβ1-40-treated cells. An enhancement of C20:4 n-6, C22:6 n-3 and saturated VLCFAs was also observed. Therefore, Aβ1-40-induced side effects are associated with intracellular accumulation of lipids, especially cholesterol, oxysterols (7β-OHC, 7KC), C20:4 n-6, and saturated VLCFAs, which could in turn contribute to neurotoxicity.
文摘Fatty acids with different chain length were deoxygenated in the absence of hydrogen (caprylic acid (CA), lauric acid (LA) and stearic acid (SA)). The catalytic tests were carried over Pd-containing catalysts out in a batch reactor under inert gas for 6 h at 250°C to 350°C and pressures from 18 to 75 bar in the absence of additionally fed hydrogen. Pd-containing catalysts were tested;the best performing catalyst was 10% Pd/C with 63% undecane yield at 327°C. These catalysts were used for a comparative decarboxylation of CA, LA and SA. At equal reaction conditions (300°C, 6 h), the chain length of the fatty acid had a strong impact on the conversion, which was steadily increasing, whereas the alkane selectivity ran through a maximum. This work demonstrated the usability of Pd-containing catalysts for the decarboxylation of various fatty acids in the absence of additionally fed hydrogen with respect to the manufacture of hydrocarbons that can be used as blending components for fuels.
基金This work is supported by Animal Nutrition,Growth and Lactation(grant no.2015-67015-23245/project accession no.1005855)from the USDA National Institute of Food and Agriculturethe North Carolina Agricultural Research Hatch projects 1016618 and 02780。
文摘To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.