{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:15:47Z","timestamp":1777652147344,"version":"3.51.4"},"reference-count":106,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T00:00:00Z","timestamp":1762560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R0HL143885"],"award-info":[{"award-number":["R0HL143885"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["P30AG066615"],"award-info":[{"award-number":["P30AG066615"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NHLBI in collaboration with the University of Alabama at Birmingham","award":["75N92023D00002"],"award-info":[{"award-number":["75N92023D00002"]}]},{"name":"NHLBI in collaboration with the University of Alabama at Birmingham","award":["75N92023D00005"],"award-info":[{"award-number":["75N92023D00005"]}]},{"DOI":"10.13039\/100007059","name":"Northwestern University","doi-asserted-by":"crossref","award":["75N92023D00004"],"award-info":[{"award-number":["75N92023D00004"]}],"id":[{"id":"10.13039\/100007059","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"crossref","award":["75N92023D00006"],"award-info":[{"award-number":["75N92023D00006"]}],"id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007241","name":"Kaiser Foundation Research Institute","doi-asserted-by":"crossref","award":["75N92023D00003"],"award-info":[{"award-number":["75N92023D00003"]}],"id":[{"id":"10.13039\/100007241","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: There are differences in lipid metabolism by sex that are relevant for health, but metabolic pathways are not fully understood. We investigated sex differences in cross-sectional associations between metabolic pathways identified using untargeted metabolomics and clinical lipid measures (total cholesterol [TC], triglycerides [TG], and low- and high-density lipoprotein cholesterol [LDL-c; HDL-c]) from blood plasma in the Coronary Artery Risk Development in Young Adults (CARDIA) study (Year 20; 2005\u20132006). Our objective was to determine whether associations between metabolic pathways and lipid measures differ by sex and to identify pathways that may underlie sex-specific mechanisms of lipid metabolism. Methods: Using data from 2169 participants, (44% women, mean age = 45, 58% White, 42% Black), we used: (1) Orthogonal partial least squares-regression (OPLS-R) to compare variation in TC, TG, LDL-c, and HDL-c explained by metabolites in men vs. women, (2) linear regression to assess sex-modification of associations between 7255 metabolite peaks and lipid measures using false discovery rate (FDR)-corrected p &lt; 0.1, and (3) pathway enrichment analyses to identify metabolic pathways that differed by sex using Fisher\u2019s exact test (FET) p &lt; 0.05. Results: We found that: (1) untargeted metabolomic data reflected variation in lipid measures better for men compared to women, (2) associations between metabolite peaks and lipid measures differed by sex, and (3) 8 unique pathways differed by sex, particularly primary bile acid biosynthesis, linoleic acid metabolism, and arginine biosynthesis. Conclusions: Our findings suggest distinct lipid-associated metabolic activity by sex that points to potential mechanistic pathways.<\/jats:p>","DOI":"10.3390\/metabo15110730","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T15:07:31Z","timestamp":1762787251000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex Modifies Metabolic Pathways Associated with Lipids in Untargeted Metabolomics: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2005\u20132006"],"prefix":"10.3390","volume":"15","author":[{"given":"Autumn G.","family":"Hullings","sequence":"first","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-8166","authenticated-orcid":false,"given":"Annie Green","family":"Howard","sequence":"additional","affiliation":[{"name":"Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA"},{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie A.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 28081, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christy L.","family":"Avery","sequence":"additional","affiliation":[{"name":"Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA"},{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-0366","authenticated-orcid":false,"given":"Kari E.","family":"North","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin","family":"Mhatre","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Sciences, Levine Cancer Institute, Atrium Health, Charlotte, NC 28204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Sciences, Levine Cancer Institute, Atrium Health, Charlotte, NC 28204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 28081, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-3270","authenticated-orcid":false,"given":"Blake R.","family":"Rushing","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 28081, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 28081, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuxia","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics & Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-5796","authenticated-orcid":false,"given":"Cora E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penny","family":"Gordon-Larsen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1001\/jama.2019.9161","article-title":"Trends in Cardiometabolic Mortality in the United States, 1999-2017","volume":"322","author":"Shah","year":"2019","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tsao, C.W., Aday, A.W., Almarzooq, Z.I., Alonso, A., Beaton, A.Z., Bittencourt, M.S., Boehme, A.K., Buxton, A.E., Carson, A.P., and Commodore-Mensah, Y. (2022). Heart Disease and Stroke Statistics\u20142022 Update: A Report from the American Heart Association. Circulation, 145.","DOI":"10.1161\/CIR.0000000000001052"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.tem.2022.02.001","article-title":"Lipids and Lipoproteins in Cardiovascular Diseases: A Classification","volume":"33","author":"Bhargava","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2020.07.019","article-title":"Lipoproteins and Lipids in Cardiovascular Disease: From Mechanistic Insights to Therapeutic Targeting","volume":"159","author":"Soppert","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1210\/jc.2010-2061","article-title":"Sex Differences in Lipid and Lipoprotein Metabolism: It\u2019s Not Just about Sex Hormones","volume":"96","author":"Wang","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1097\/MOL.0000000000000536","article-title":"Sex Differences in Metabolism and Cardiometabolic Disorders","volume":"29","author":"Mehrabian","year":"2018","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1161\/CIRCRESAHA.120.315930","article-title":"Sex as a Biological Variable in Atherosclerosis","volume":"126","author":"Man","year":"2020","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1016\/S0140-6736(21)00684-X","article-title":"The Lancet Women and Cardiovascular Disease Commission: Reducing the Global Burden by 2030","volume":"397","author":"Vogel","year":"2021","journal-title":"The Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update: A Report from the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s11883-005-0065-6","article-title":"Gender Differences in Lipoprotein Metabolism and Dietary Response: Basis in Hormonal Differences and Implications for Cardiovascular Disease","volume":"7","author":"Knopp","year":"2005","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wu, B.N., and O\u2019Sullivan, A.J. (2011). Sex Differences in Energy Metabolism Need to Be Considered with Lifestyle Modifications in Humans. J. Nutr. Metab., 2011.","DOI":"10.1155\/2011\/391809"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12937-015-0035-y","article-title":"Sex Differences in the Impact of the Mediterranean Diet on Systemic Inflammation","volume":"14","author":"Lamarche","year":"2015","journal-title":"Nutr. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Artegoitia, V.M., Krishnan, S., Bonnel, E.L., Stephensen, C.B., Keim, N.L., and Newman, J.W. (2021). Healthy Eating Index Patterns in Adults by Sex and Age Predict Cardiometabolic Risk Factors in a Cross-Sectional Study. BMC Nutr., 7.","DOI":"10.1186\/s40795-021-00432-4"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jprot.2017.11.001","article-title":"Gender-Related Metabolomics and Lipidomics: From Experimental Animal Models to Clinical Evidence","volume":"178","author":"Audano","year":"2018","journal-title":"J. Proteom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1089\/omi.2013.0031","article-title":"Race and Sex Differences in Small-Molecule Metabolites and Metabolic Hormones in Overweight and Obese Adults","volume":"17","author":"Patel","year":"2013","journal-title":"OMICS"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1161\/CIRCULATIONAHA.113.008507","article-title":"Effects of Sex on Coronary Microvascular Dysfunction and Cardiac Outcomes","volume":"129","author":"Murthy","year":"2014","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1093\/ajcn\/76.6.1261","article-title":"Diet Quality and Major Chronic Disease Risk in Men and Women: Moving toward Improved Dietary Guidance","volume":"76","author":"McCullough","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1503\/cmaj.051455","article-title":"A Comprehensive View of Sex-Specific Issues Related to Cardiovascular Disease","volume":"176","author":"Pilote","year":"2007","journal-title":"Can. Med. Assoc. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmet.2018.05.008","article-title":"Sex Differences in Lipid and Lipoprotein Metabolism","volume":"15","author":"Palmisano","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Robinson, G.A., Pineda-Torra, I., Ciurtin, C., and Jury, E.C. (2022). Sex Differences in Lipid Metabolism: Implications for Systemic Lupus Erythematosus and Cardiovascular Disease Risk. Front. Med., 9.","DOI":"10.3389\/fmed.2022.914016"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1373\/clinchem.2004.032763","article-title":"Sex and Age Differences in Lipoprotein Subclasses Measured by Nuclear Magnetic Resonance Spectroscopy: The Framingham Study","volume":"50","author":"Freedman","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Psychogios, N., Hau, D.D., Peng, J., Guo, A.C., Mandal, R., Bouatra, S., Sinelnikov, I., Krishnamurthy, R., Eisner, R., and Gautam, B. (2011). The Human Serum Metabolome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016957"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s11306-015-0829-0","article-title":"Gender-Specific Pathway Differences in the Human Serum Metabolome","volume":"11","author":"Krumsiek","year":"2015","journal-title":"Metabolomics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tabassum, R., Ruotsalainen, S., Ottensmann, L., Gerl, M.J., Klose, C., Tukiainen, T., Pirinen, M., Simons, K., Wid\u00e9n, E., and Ripatti, S. (2022). Lipidome- and Genome-Wide Study to Understand Sex Differences in Circulatory Lipids. J. Am. Heart Assoc., 11.","DOI":"10.1161\/JAHA.122.027103"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/0895-4356(88)90080-7","article-title":"Cardia: Study Design, Recruitment, and Some Characteristics of the Examined Subjects","volume":"41","author":"Friedman","year":"1988","journal-title":"J. Clin. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.conctc.2017.12.003","article-title":"Where Are They Now? Retention Strategies over 25 Years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study","volume":"9","author":"Funkhouser","year":"2018","journal-title":"Contemp. Clin. Trials Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jacc.2021.05.022","article-title":"The Coronary Artery Risk Development in Young Adults (CARDIA) Study","volume":"78","author":"Lewis","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wei, R., Wang, J., Su, M., Jia, E., Chen, S., Chen, T., and Ni, Y. (2018). Missing Value Imputation Approach for Mass Spectrometry-Based Metabolomics Data. Sci. Rep., 8.","DOI":"10.1038\/s41598-017-19120-0"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/bioinformatics\/btr597","article-title":"MissForest\u2014Non-Parametric Missing Value Imputation for Mixed-Type Data","volume":"28","author":"Stekhoven","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8696","DOI":"10.1021\/acs.analchem.7b00947","article-title":"One Step Forward for Reducing False Positive and False Negative Compound Identifications from Mass Spectrometry Metabolomics Data: New Algorithms for Constructing Extracted Ion Chromatograms and Detecting Chromatographic Peaks","volume":"89","author":"Myers","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41398-021-01228-7","article-title":"Metabolomics Reveals Biomarkers of Opioid Use Disorder","volume":"11","author":"Ghanbari","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_32","first-page":"12","article-title":"Methods of Metabolite Identification Using MS\/MS Data","volume":"62","author":"Kwak","year":"2022","journal-title":"J. Comput. Inf. Syst."},{"key":"ref_33","unstructured":"Hullings, A.G. (2024). Sex Differences in Dietary Intake in Association with Cardiovascular Disease-Related Lipid Metabolites. [Ph.D. Thesis, The University of North Carolina at Chapel Hill]."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Behbodikhah, J., Ahmed, S., Elyasi, A., Kasselman, L.J., De Leon, J., Glass, A.D., and Reiss, A.B. (2021). Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites, 11.","DOI":"10.3390\/metabo11100690"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur Heart J"},{"key":"ref_36","first-page":"656","article-title":"Distribution of Lipoproteins and Apolipoproteins in Young Adults the CARDIA Study","volume":"9","author":"Donahue","year":"1989","journal-title":"Arterioscler. Off. J. Am. Heart Assoc. Inc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1517\/17425255.3.3.441","article-title":"Ezetimibe: An Update on the Mechanism of Action, Pharmacokinetics and Recent Clinical Trials","volume":"3","author":"Sweeney","year":"2007","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"National Cholesterol Education Program NCEP Expert Panel (2002). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation, 106, 3143\u20133421.","DOI":"10.1161\/circ.106.25.3143"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wu, J., Province, M.A., Coon, H., Hunt, S.C., Eckfeldt, J.H., Arnett, D.K., Heiss, G., Lewis, C.E., Ellison, R.C., and Rao, D.C. (2007). An Investigation of the Effects of Lipid-Lowering Medications: Genome-Wide Linkage Analysis of Lipids in the HyperGEN Study. BMC Genet., 8.","DOI":"10.1186\/1471-2156-8-60"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/00008483-198911000-00003","article-title":"Validity and Reliability of Short Physical Activity History","volume":"9","author":"Jacobs","year":"1989","journal-title":"J. Cardiopulm. Rehabil."},{"key":"ref_41","first-page":"15","article-title":"A Study of the Reliability and Comparative Validity of the Cardia Dietary History","volume":"4","author":"Liu","year":"1994","journal-title":"Ethn. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A New Equation to Estimate Glomerular Filtration Rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"580","DOI":"10.3945\/ajcn.111.020719","article-title":"Longitudinal Trends in Diet and Effects of Sex, Race, and Education on Dietary Quality Score Change: The Coronary Artery Risk Development in Young Adults Study","volume":"95","author":"Sijtsma","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/oxfordjournals.aje.a115807","article-title":"Diet, Body Size, and Plasma Lipids-Lipoproteins in Young Adults: Differences by Race and Sex","volume":"133","author":"Ballew","year":"1991","journal-title":"Am. J. Epidemiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/jn\/nxaa338","article-title":"Serum Metabolites Associated with Healthy Diets in African Americans and European Americans","volume":"151","author":"Kim","year":"2021","journal-title":"J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"411","DOI":"10.22436\/jmcs.08.04.09","article-title":"Applications of Opls Statistical Method in Medicine","volume":"08","author":"Vajargah","year":"2014","journal-title":"J. Math. Comput. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ghosh, T., Zhang, W., Ghosh, D., and Kechris, K. (2020). Predictive Modeling for Metabolomics Data. Computational Methods and Data Analysis for Metabolomics, Springer.","DOI":"10.1007\/978-1-0716-0239-3_16"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1021\/acs.jproteome.8b00019","article-title":"Target-Decoy-Based False Discovery Rate Estimation for Large-Scale Metabolite Identification","volume":"17","author":"Wang","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s41467-017-01318-5","article-title":"Significance Estimation for Large Scale Metabolomics Annotations by Spectral Matching","volume":"8","author":"Scheubert","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2010). Standards of Medical Care in Diabetes\u20142010. Diabetes Care, 33, S11\u2013S61.","DOI":"10.2337\/dc10-S011"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1161\/01.HYP.0000107251.49515.c2","article-title":"Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure","volume":"42","author":"Chobanian","year":"2003","journal-title":"Hypertension"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"McGranaghan, P., Kirwan, J.A., Garcia-Rivera, M.A., Pieske, B., Edelmann, F., Blaschke, F., Appunni, S., Saxena, A., Rubens, M., and Veledar, E. (2021). Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies. Metabolites, 11.","DOI":"10.3390\/metabo11090621"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lu, Y., Pang, Z., and Xia, J. (2023). Comprehensive Investigation of Pathway Enrichment Methods for Functional Interpretation of LC\u2013MS Global Metabolomics Data. Brief. Bioinform., 24.","DOI":"10.1093\/bib\/bbac553"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"458","DOI":"10.5114\/aoms\/157308","article-title":"Menopause and Women\u2019s Cardiovascular Health: Is It Really an Obvious Relationship?","volume":"19","author":"Ryczkowska","year":"2023","journal-title":"Arch. Med. Sci."},{"key":"ref_56","first-page":"e506","article-title":"Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement from the American Heart Association","volume":"142","author":"Aggarwal","year":"2020","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1097\/EDE.0b013e3181577654","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement","volume":"18","author":"Altman","year":"2007","journal-title":"Epidemiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the Gap between Raw Spectra and Functional Insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.3945\/ajcn.116.130492","article-title":"Plasma Acylcarnitines and Risk of Cardiovascular Disease: Effect of Mediterranean Diet Interventions","volume":"103","author":"Zheng","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fei, N., Bernab\u00e9, B.P., Lie, L., Baghdan, D., Bedu-Addo, K., Plange-Rhule, J., Forrester, T.E., Lambert, E.V., Bovet, P., and Gottel, N. (2019). The Human Microbiota Is Associated with Cardiometabolic Risk across the Epidemiologic Transition. PLoS ONE, 14.","DOI":"10.1101\/595934"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6793346","DOI":"10.1155\/2022\/6793346","article-title":"Exploration of the Mechanism of Linoleic Acid Metabolism Dysregulation in Metabolic Syndrome","volume":"2022","author":"Wen","year":"2022","journal-title":"Genet. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1161\/CIRCULATIONAHA.114.010236","article-title":"Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies","volume":"130","author":"Farvid","year":"2014","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e003970","DOI":"10.1161\/JAHA.116.003970","article-title":"Microbiota-Dependent Metabolite Trimethylamine N-Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)","volume":"5","author":"Meyer","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Canyelles, M., Borr\u00e0s, C., Rotllan, N., Tondo, M., Escol\u00e0-Gil, J.C., and Blanco-Vaca, F. (2023). Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031940"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cmet.2012.12.011","article-title":"Trimethylamine-N-Oxide, a Metabolite Associated with Atherosclerosis, Exhibits Complex Genetic and Dietary Regulation","volume":"17","author":"Bennett","year":"2013","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1093\/nutrit\/nuaa111","article-title":"Gut Microbiota\u2013Associated Trimethylamine N-Oxide and Increased Cardiometabolic Risk in Adults: A Systematic Review and Dose-Response Meta-Analysis","volume":"79","author":"Vajdi","year":"2021","journal-title":"Nutr. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/ije\/dyx234","article-title":"Dietary Glutamine, Glutamate and Mortality: Two Large Prospective Studies in US Men and Women","volume":"47","author":"Ma","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.3748\/wjg.v18.i29.3775","article-title":"Alanine and Aspartate Aminotransferase and Glutamine-Cycling Pathway: Their Roles in Pathogenesis of Metabolic Syndrome","volume":"18","author":"Sookoian","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Berkowitz, L., Salazar, C., Ryff, C.D., Coe, C.L., and Rigotti, A. (2022). Serum Sphingolipid Profiling as a Novel Biomarker for Metabolic Syndrome Characterization. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.1092331"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI131838","article-title":"Machine Learning Reveals Serum Sphingolipids as Cholesterol-Independent Biomarkers of Coronary Artery Disease","volume":"130","author":"Poss","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrendo.2016.169","article-title":"Sphingolipids and Phospholipids in Insulin Resistance and Related Metabolic Disorders","volume":"13","author":"Meikle","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1161\/CIRCULATIONAHA.123.065409","article-title":"Ceramides and Atherosclerotic Cardiovascular Disease: A Current Perspective","volume":"149","author":"Zhu","year":"2024","journal-title":"Circulation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/s41467-022-28496-1","article-title":"Dihydroceramide- and Ceramide-Profiling Provides Insights into Human Cardiometabolic Disease Etiology","volume":"13","author":"Wittenbecher","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Sheng, L., Jena, P.K., Liu, H.-X., Kalanetra, K.M., Gonzalez, F.J., French, S.W., Krishnan, V.V., Mills, D.A., and Wan, Y.-J.Y. (2017). Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-01576-9"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Phelps, T., Snyder, E., Rodriguez, E., Child, H., and Harvey, P. (2019). The Influence of Biological Sex and Sex Hormones on Bile Acid Synthesis and Cholesterol Homeostasis. Biol. Sex. Differ., 10.","DOI":"10.1186\/s13293-019-0265-3"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Baars, A., Oosting, A., Lohuis, M., Koehorst, M., El Aidy, S., Hugenholtz, F., Smidt, H., Mischke, M., Boekschoten, M.V., and Verkade, H.J. (2018). Sex Differences in Lipid Metabolism Are Affected by Presence of the Gut Microbiota. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31695-w"},{"key":"ref_77","first-page":"261","article-title":"The Role of Bile Acids in Cardiovascular Diseases: From Mechanisms to Clinical Implications","volume":"14","author":"Zhang","year":"2023","journal-title":"Aging Dis."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gheorghe, G., Toth, P.P., Bungau, S., Behl, T., Ilie, M., Pantea Stoian, A., Bratu, O.G., Bacalbasa, N., Rus, M., and Diaconu, C.C. (2020). Cardiovascular Risk and Statin Therapy Considerations in Women. Diagnostics, 10.","DOI":"10.3390\/diagnostics10070483"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.jacc.2018.02.032","article-title":"Sex Differences in High-Intensity Statin Use Following Myocardial Infarction in the United States","volume":"71","author":"Peters","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"398","DOI":"10.7326\/M13-1788","article-title":"Association of Dietary, Circulating, and Supplement Fatty Acids with Coronary Risk","volume":"160","author":"Chowdhury","year":"2014","journal-title":"Ann. Intern. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/CIR.0000000000000510","article-title":"Dietary Fats and Cardiovascular Disease: A Presidential Advisory from the American Heart Association","volume":"136","author":"Sacks","year":"2017","journal-title":"Circulation"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.3945\/ajcn.115.116046","article-title":"Dietary Fat Intake and Risk of Cardiovascular Disease and All-Cause Mortality in a Population at High Risk of Cardiovascular Disease","volume":"102","author":"Babio","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1186\/s12967-023-04726-y","article-title":"Sex Differences in the Association between Plasma Polyunsaturated Fatty Acids Levels and Moderate-to-Severe Plaque Psoriasis Severity: A Cross-Sectional and Longitudinal Study","volume":"21","author":"Wang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1093\/ajcn\/80.5.1167","article-title":"Docosahexaenoic Acid Concentrations Are Higher in Women than in Men Because of Estrogenic Effects","volume":"80","author":"Giltay","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1017\/S0029665108005983","article-title":"Gender Differences in the n-3 Fatty Acid Content of Tissues","volume":"67","author":"Childs","year":"2008","journal-title":"Proc. Nutr. Soc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.plefa.2013.05.003","article-title":"Treatment of Ovariectomized Rats with 17\u03b2-Estradiol Increases Hepatic Delta-6 Desaturase Enzyme Expression and Docosahexaenoic Acid Levels in Hepatic and Plasma Phospholipids","volume":"89","author":"Kitson","year":"2013","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_88","first-page":"158","article-title":"Gender-Related Differences in Lifestyle May Affect Health Status","volume":"52","author":"Scazzocchio","year":"2016","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Wiels\u00f8e, M., Berthelsen, D., Mulvad, G., Isidor, S., Long, M., and Bonefeld-J\u00f8rgensen, E.C. (2021). Dietary Habits among Men and Women in West Greenland: Follow-up on the ACCEPT Birth Cohort. BMC Public Health, 21.","DOI":"10.1186\/s12889-021-11359-7"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1017\/S0007114511006969","article-title":"Sex Differences in the Impact of the Mediterranean Diet on Cardiovascular Risk Profile","volume":"108","author":"Riverin","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.3390\/nu7053705","article-title":"Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation","volume":"7","author":"Corneau","year":"2015","journal-title":"Nutrients"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Costanzo, M., Caterino, M., Sotgiu, G., Ruoppolo, M., Franconi, F., and Campesi, I. (2022). Sex Differences in the Human Metabolome. Biol. Sex. Differ., 13.","DOI":"10.1186\/s13293-022-00440-4"},{"key":"ref_93","first-page":"614","article-title":"Serum Metabolomic Profiles Suggest Influence of Sex and Oral Contraceptive Use","volume":"6","author":"Ruoppolo","year":"2014","journal-title":"Am. J. Transl. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1248\/bpb.b16-00226","article-title":"Gender- and Age-Associated Differences in Serum Metabolite Profiles among Japanese Populations","volume":"39","author":"Saito","year":"2016","journal-title":"Biol. Pharm. Bull."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Andraos, S., Lange, K., Clifford, S.A., Jones, B., Thorstensen, E.B., Wake, M., Burgner, D.P., Saffery, R., and O\u2019Sullivan, J.M. (2021). Population Epidemiology and Concordance for Plasma Amino Acids and Precursors in 11\u201312-Year-Old Children and Their Parents. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80923-9"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/gerona\/glv074","article-title":"Human Aging Is a Metabolome-Related Matter of Gender","volume":"71","author":"Pamplona","year":"2016","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1021\/acs.jproteome.7b00404","article-title":"Age and Sex Effects on Plasma Metabolite Association Networks in Healthy Subjects","volume":"17","author":"Vignoli","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Rist, M.J., Roth, A., Frommherz, L., Weinert, C.H., Kr\u00fcger, R., Merz, B., Bunzel, D., Mack, C., Egert, B., and Bub, A. (2017). Metabolite Patterns Predicting Sex and Age in Participants of the Karlsruhe Metabolomics and Nutrition (KarMeN) Study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183228"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ab.2006.02.033","article-title":"Probing Gender-Specific Metabolism Differences in Humans by Nuclear Magnetic Resonance-Based Metabonomics","volume":"352","author":"Kochhar","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11306-014-0707-1","article-title":"Molecular Phenotyping of a UK Population: Defining the Human Serum Metabolome","volume":"11","author":"Dunn","year":"2015","journal-title":"Metabolomics"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Mittelstrass, K., Ried, J.S., Yu, Z., Krumsiek, J., Gieger, C., Prehn, C., Roemisch-Margl, W., Polonikov, A., Peters, A., and Theis, F.J. (2011). Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002215"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Gieger, C., Geistlinger, L., Altmaier, E., Hrab\u00e9 de Angelis, M., Kronenberg, F., Meitinger, T., Mewes, H.-W., Wichmann, H.-E., Weinberger, K.M., and Adamski, J. (2008). Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000282"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev-nutr-071816-064827","article-title":"Genetic Basis for Sex Differences in Obesity and Lipid Metabolism","volume":"37","author":"Link","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1038\/s41591-022-02014-8","article-title":"Influence of the Microbiome, Diet and Genetics on Inter-Individual Variation in the Human Plasma Metabolome","volume":"28","author":"Chen","year":"2022","journal-title":"Nat. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/s42255-022-00670-1","article-title":"Genome-Microbiome Interplay Provides Insight into the Determinants of the Human Blood Metabolome","volume":"4","author":"Diener","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ke, C., Hou, Y., Zhang, H., Yang, K., Wang, J., Guo, B., Zhang, F., Li, H., Zhou, X., and Li, Y. (2015). Plasma Metabolic Profiles in Women Are Menopause Dependent. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141743"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/11\/730\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T05:30:52Z","timestamp":1762839052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/11\/730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,8]]},"references-count":106,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["metabo15110730"],"URL":"https:\/\/doi.org\/10.3390\/metabo15110730","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,8]]}}}