BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innat...BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.展开更多
Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hund...Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.展开更多
In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and mayprovide more detailed information on the fertility status of the respective donor. Give...In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and mayprovide more detailed information on the fertility status of the respective donor. Given the intra-individual variability of spermiogramparameters between two donations, this study sought to elucidate the biological variability of the seminal plasma metabolome overan average period of 8 weeks. Two time-shifted semen samples from 15 healthy donors were compared by a targeted metabolomicsapproach utilizing the Biocrates AbsoluteIDQ p180 kit. Next to intraclass correlation coefficients (ICC), which represent a measureof reliability, coefficients of variation within individuals(CVW) and coefficients of variation between individuals (CVB) were calculatedfor each metabolite to demonstrate its stability. Furthermore, men were divided into two cohorts, a similar sperm concentration(SSC) and a differing sperm concentration (DSC) cohort, based on the observed variance in sperm concentration between the twosemen donations. The ICC was higher in the SSC compared to the DSC cohort. The levels of 18 metabolites, primarily acylcarnitines,varied between the initial and subsequent donations. After subdivision into subgroups, only ornithine and phosphatidylcholine 40:5exhibited differential levels between the two donations in the SSC group, compared to 14 metabolites in the DSCgroup.CVBwashigher than CVW but both differed between the metabolite subclasses. Biogenic amines were identified as the least reliable analytesover time, exhibiting the highest CVW,compared to sphingomyelins, which demonstrated the highest reliability with the lowestvariation.CVB was the highest for ether-bound glycerophosphatidylcholines and the lowest for amino acids.展开更多
BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarniti...BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate these differences.展开更多
The World Health Organization has stated that obesity in childhood is one of themost serious public health challenges of the 21st century. Overweightness andobesity in early childhood lead to a higher risk of overweig...The World Health Organization has stated that obesity in childhood is one of themost serious public health challenges of the 21st century. Overweightness andobesity in early childhood lead to a higher risk of overweightness and obesity inadulthood, thus conferring an increased risk of chronic inflammatory conditions,including type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fattyliver disease, and some cancers. Therefore, metabolome analysis, targeted atscreening and intervening in childhood obesity, is very important. Recent studieshave indicated that amino acid and lipid metabolism could influence metabolicpathways in children with obesity. For this review, we searched clinical dataaddressing metabolomic profiles and insulin resistance (IR) in children withobesity from inception to February 2021 in Medline, Web of Science, and Scopus.According to our search, branched-chain amino acids (BCAAs), aromatic aminoacids, and acylcarnitines have reportedly been associated with IR as biomarkersfor diabetes in children. BCAAs, tyrosine, and phenylalanine could be predictorsof the future development of diabetes in nondiabetic subjects. In addition, it iswell known that insulin regulates BCAA metabolism, and BCAA is a biomarkerfor IR. To interpret the mechanism behind metabolic changes in obesity, it is veryimportant to understand the pathways and combinations related with amino acid,lipid and glucose metabolism. In this review, we summarize studies on metabolicchanges to understand metabolomics in children with obesity.展开更多
Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans.Carnitine-acylcarnitine translocase deficiency(CACTD)is a scarce autosomal recessive genetic disease and may result in patients’d...Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans.Carnitine-acylcarnitine translocase deficiency(CACTD)is a scarce autosomal recessive genetic disease and may result in patients’death due to heart arrest or respiratory insufficiency.However,the reasons and mechanism of CACTD inducing respiratory insufficiency have never been elucidated.Herein,we employed lipidomic techniques to create comprehensive lipidomic maps of entire lungs throughout both prenatal and postnatal developmental stages in mice.We found that the acylcarnitines manifested notable variations and coordinated the expression levels of carnitine-acylcarnitine translocase(Cact)across these lung developmental stages.Cact-null mice were all dead with a symptom of respiratory distress and exhibited failed lung development.Loss of Cact resulted in an accumulation of palmitoyl-carnitine(C16-acylcarnitine)in the lungs and promoted the proliferation of mesenchymal progenitor cells.Mesenchymal cells with elevated C16-acylcarnitine levels displayed minimal changes in energy metabolism but,upon investigation,revealed an interaction with sterile alpha motif domain and histidine-aspartate domain-containing protein 1(Samhd1),leading to decreased protein abundance and enhanced cell proliferation.Thus,our findings present a mechanism addressing respiratory distress in CACTD,offering a valuable reference point for both the elucidation of pathogenesis and the exploration of treatment strategies for neonatal respiratory distress.展开更多
Despite therapy with potent antiviral agents,chronic hepatitis B(CHB)patients remain at high risk of hepatocellular carcinoma(HCC).While metabolites have been rediscovered as active drivers of biological processes inc...Despite therapy with potent antiviral agents,chronic hepatitis B(CHB)patients remain at high risk of hepatocellular carcinoma(HCC).While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis,the specific metabolites modulating HCC risk in CHB patients are largely unknown.Here,we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale,prospective cohort.Metabolomics analysis reveals a reduction in long-chain acylcarnitines(LCACs)in the baseline plasma of patients with HCC development.LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity.Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A,which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway.Indeed,blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients.The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control.These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.展开更多
Gestational diabetes mellitus(GDM)is a high-prevalence disease and diagnosed in middle pregnancy.Acylcarnitines are a series of fatty acid esters of carnitine and play important roles in fatty acid and carbohydrate me...Gestational diabetes mellitus(GDM)is a high-prevalence disease and diagnosed in middle pregnancy.Acylcarnitines are a series of fatty acid esters of carnitine and play important roles in fatty acid and carbohydrate metabolism.However,the role of acylcarnitine on the development of GDM remains unclear.This case-control study involving 214 study participants(107 GDM cases and 107 matched controls)was conducted in a cohort,in China,from 2013 to 2015.The levels of carnitine and 36 acylcarnitines in serum samples collected at the early stage of pregnancy were determined by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry.The associations of the levels of the 37 targeted compounds with GDM risk were investigated by using binary conditional logistic regression models.Alterations in acylcarnitine levels were observed 9–17 weeks before GDM diagnosis.The increases in levels of propionyl-carnitine,malonyl-carnitine,isovaleryl-carnitine,palmitoyl-carnitine and linoleoyl-carnitine were associated with GDM risk with odds ratios(ORs)per standard deviation(SD)increment greater than 1(p<0.05),after adjustment for potential confounding factors(pre-pregnancy body mass index and parity).On the contrary,the increases of decanoyl-carnitine,decenoyl-carnitine,tetradecenoyl-carnitine,tetradecandienoylcarnitine levels were associated with the reduced risk for GDM(ORs per SD<1,p<0.05).To our knowledge,the present study is the largest case-control study to investigate the association between early-pregnancy acylcarnitine levels in serum and GDM risk.The findings add to the evidence for the association between acylcarnitine levels and GDM risk.展开更多
基金National Natural Science Foundation of China,No.81773931Beijing Municipal Administration of Hospitals’ Youth Program,No.QML20170105Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support "Yangfan" Project,No.ZYLX201804
文摘BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.
基金financial supports from the National Key R&D Program of China(Grant Nos.:2022YFC3400700,2022YFA0806400,and 2020YFE0201600)Shanghai Municipal Science and Technology Major Project(Grant No.:2017SHZDZX01)the National Natural Science Foundation of China(Grant No.:31821002).
文摘Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.
文摘In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and mayprovide more detailed information on the fertility status of the respective donor. Given the intra-individual variability of spermiogramparameters between two donations, this study sought to elucidate the biological variability of the seminal plasma metabolome overan average period of 8 weeks. Two time-shifted semen samples from 15 healthy donors were compared by a targeted metabolomicsapproach utilizing the Biocrates AbsoluteIDQ p180 kit. Next to intraclass correlation coefficients (ICC), which represent a measureof reliability, coefficients of variation within individuals(CVW) and coefficients of variation between individuals (CVB) were calculatedfor each metabolite to demonstrate its stability. Furthermore, men were divided into two cohorts, a similar sperm concentration(SSC) and a differing sperm concentration (DSC) cohort, based on the observed variance in sperm concentration between the twosemen donations. The ICC was higher in the SSC compared to the DSC cohort. The levels of 18 metabolites, primarily acylcarnitines,varied between the initial and subsequent donations. After subdivision into subgroups, only ornithine and phosphatidylcholine 40:5exhibited differential levels between the two donations in the SSC group, compared to 14 metabolites in the DSCgroup.CVBwashigher than CVW but both differed between the metabolite subclasses. Biogenic amines were identified as the least reliable analytesover time, exhibiting the highest CVW,compared to sphingomyelins, which demonstrated the highest reliability with the lowestvariation.CVB was the highest for ether-bound glycerophosphatidylcholines and the lowest for amino acids.
文摘BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate these differences.
文摘The World Health Organization has stated that obesity in childhood is one of themost serious public health challenges of the 21st century. Overweightness andobesity in early childhood lead to a higher risk of overweightness and obesity inadulthood, thus conferring an increased risk of chronic inflammatory conditions,including type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fattyliver disease, and some cancers. Therefore, metabolome analysis, targeted atscreening and intervening in childhood obesity, is very important. Recent studieshave indicated that amino acid and lipid metabolism could influence metabolicpathways in children with obesity. For this review, we searched clinical dataaddressing metabolomic profiles and insulin resistance (IR) in children withobesity from inception to February 2021 in Medline, Web of Science, and Scopus.According to our search, branched-chain amino acids (BCAAs), aromatic aminoacids, and acylcarnitines have reportedly been associated with IR as biomarkersfor diabetes in children. BCAAs, tyrosine, and phenylalanine could be predictorsof the future development of diabetes in nondiabetic subjects. In addition, it iswell known that insulin regulates BCAA metabolism, and BCAA is a biomarkerfor IR. To interpret the mechanism behind metabolic changes in obesity, it is veryimportant to understand the pathways and combinations related with amino acid,lipid and glucose metabolism. In this review, we summarize studies on metabolicchanges to understand metabolomics in children with obesity.
基金supported by the National Key R&D Program of China(2022YFC3600202 and 2018YFA0800902)the National Natural Science Foundation of China(32170843)the Major Project of Guangzhou National Laboratory(Grant No.GZNL2024A03013).
文摘Disruption of acylcarnitine homeostasis results in life-threatening outcomes in humans.Carnitine-acylcarnitine translocase deficiency(CACTD)is a scarce autosomal recessive genetic disease and may result in patients’death due to heart arrest or respiratory insufficiency.However,the reasons and mechanism of CACTD inducing respiratory insufficiency have never been elucidated.Herein,we employed lipidomic techniques to create comprehensive lipidomic maps of entire lungs throughout both prenatal and postnatal developmental stages in mice.We found that the acylcarnitines manifested notable variations and coordinated the expression levels of carnitine-acylcarnitine translocase(Cact)across these lung developmental stages.Cact-null mice were all dead with a symptom of respiratory distress and exhibited failed lung development.Loss of Cact resulted in an accumulation of palmitoyl-carnitine(C16-acylcarnitine)in the lungs and promoted the proliferation of mesenchymal progenitor cells.Mesenchymal cells with elevated C16-acylcarnitine levels displayed minimal changes in energy metabolism but,upon investigation,revealed an interaction with sterile alpha motif domain and histidine-aspartate domain-containing protein 1(Samhd1),leading to decreased protein abundance and enhanced cell proliferation.Thus,our findings present a mechanism addressing respiratory distress in CACTD,offering a valuable reference point for both the elucidation of pathogenesis and the exploration of treatment strategies for neonatal respiratory distress.
基金supported by National Key Research and Development Program of China(2022YFC2304800)National Natural Science Foundation of China(U22A20274 and 82203305)+1 种基金Guangdong Basic and Applied Basic Research Foundation of Guangzhou Joint Fund(2022B1515120039,China)Science and Technology Projects in Guangzhou(2024B03J0326,China).
文摘Despite therapy with potent antiviral agents,chronic hepatitis B(CHB)patients remain at high risk of hepatocellular carcinoma(HCC).While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis,the specific metabolites modulating HCC risk in CHB patients are largely unknown.Here,we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale,prospective cohort.Metabolomics analysis reveals a reduction in long-chain acylcarnitines(LCACs)in the baseline plasma of patients with HCC development.LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity.Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A,which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway.Indeed,blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients.The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control.These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.
基金supported by the National Natural Science Foundation of China(21437002)the General Research Fund(12319716)from Research Grants Council of Hong Kong
文摘Gestational diabetes mellitus(GDM)is a high-prevalence disease and diagnosed in middle pregnancy.Acylcarnitines are a series of fatty acid esters of carnitine and play important roles in fatty acid and carbohydrate metabolism.However,the role of acylcarnitine on the development of GDM remains unclear.This case-control study involving 214 study participants(107 GDM cases and 107 matched controls)was conducted in a cohort,in China,from 2013 to 2015.The levels of carnitine and 36 acylcarnitines in serum samples collected at the early stage of pregnancy were determined by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry.The associations of the levels of the 37 targeted compounds with GDM risk were investigated by using binary conditional logistic regression models.Alterations in acylcarnitine levels were observed 9–17 weeks before GDM diagnosis.The increases in levels of propionyl-carnitine,malonyl-carnitine,isovaleryl-carnitine,palmitoyl-carnitine and linoleoyl-carnitine were associated with GDM risk with odds ratios(ORs)per standard deviation(SD)increment greater than 1(p<0.05),after adjustment for potential confounding factors(pre-pregnancy body mass index and parity).On the contrary,the increases of decanoyl-carnitine,decenoyl-carnitine,tetradecenoyl-carnitine,tetradecandienoylcarnitine levels were associated with the reduced risk for GDM(ORs per SD<1,p<0.05).To our knowledge,the present study is the largest case-control study to investigate the association between early-pregnancy acylcarnitine levels in serum and GDM risk.The findings add to the evidence for the association between acylcarnitine levels and GDM risk.
