{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:51:47Z","timestamp":1782899507745,"version":"3.54.5"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai\u2019s Top Priority Research Center Construction Project","award":["2023ZZ02002"],"award-info":[{"award-number":["2023ZZ02002"]}]},{"name":"Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai","award":["GWVI-11.1-36"],"award-info":[{"award-number":["GWVI-11.1-36"]}]},{"name":"Shanghai Commission of Science and Technology","award":["21DZ2201600"],"award-info":[{"award-number":["21DZ2201600"]}]},{"name":"Shanghai Commission of Science and Technology","award":["20DZ2270900"],"award-info":[{"award-number":["20DZ2270900"]}]},{"name":"Shanghai Commission of Science and Technology","award":["21XD1401900"],"award-info":[{"award-number":["21XD1401900"]}]},{"DOI":"10.13039\/100020732","name":"Innovative Research Team of High-Level Local Universities in Shanghai","doi-asserted-by":"crossref","award":["SHSMU-ZLCX20210200"],"award-info":[{"award-number":["SHSMU-ZLCX20210200"]}],"id":[{"id":"10.13039\/100020732","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2706700"],"award-info":[{"award-number":["2024YFC2706700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171623"],"award-info":[{"award-number":["82171623"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301839"],"award-info":[{"award-number":["82301839"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571885"],"award-info":[{"award-number":["82571885"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, exhibits dysregulated lipid metabolism with distinct alterations in long-chain fatty acids (LCFAs) profile. Heterogeneous profile of LCFAs dysregulation manifest in distinct PCOS phenotypes: Saturated fatty acids (SFAs) preferentially accumulate in serum and follicular fluid (FF) of insulin-resistant\/hyperandrogenic (IR\/HA) subtypes, exacerbating lipotoxicity, inflammatory responses, and ovarian impairment; monounsaturated fatty acids (MUFAs) display compensatory elevation yet demonstrate context-dependent effects regulated by stearoyl-CoA desaturase-1 (SCD1) activity; and polyunsaturated fatty acids (PUFAs) exhibit subtype-dependent actions: n-3 derivatives (EPA\/DHA) ameliorate metabolic dysfunction, resolve inflammation, and enhance ovarian competence, whereas pro-inflammatory n-6 PUFAs elevate the n-6\/n-3 ratio, disrupting follicular homeostasis. In PCOS, dysregulation of LCFA transport receptors, including fatty acid-binding proteins 4\/5 (FABP4\/5), CD36, are associated with insulin resistance (IR) and hyperandrogenemia (HA) through obesity-independent mechanisms. Sensing receptors GPR120 and GPR40 critically orchestrate insulin sensitivity, inflammatory cascades, and reproductive function, highlighting their therapeutic relevance in PCOS pathophysiology. Although direct evidence remains limited, targeting these pathways may represent a promising strategy to concurrently mitigate HA, IR, and dyslipidemia in a phenotype-specific manner, warranting further preclinical and clinical investigations. Future investigations should focus on defining and validating clinical biomarkers, tissue-specific receptor functions, and evaluating targeted interventions in distinct PCOS phenotypes.<\/jats:p>","DOI":"10.3389\/fnut.2026.1797101","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:41:04Z","timestamp":1782898864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-chain fatty acids as functional modulators in PCOS: metabolic crosstalk, signaling pathways, and therapeutic implications"],"prefix":"10.3389","volume":"13","author":[{"given":"Cong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University","place":["Jinan, Shandong, China"]},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhi","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.fertnstert.2023.07.025","article-title":"Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"120","author":"Teede","year":"2023","journal-title":"Fertil Steril"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e1003132","DOI":"10.1371\/journal.pmed.1003132","article-title":"Distinct subtypes of polycystic ovary syndrome with novel genetic associations: an unsupervised, phenotypic clustering analysis","volume":"17","author":"Dapas","year":"2020","journal-title":"PLoS Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/s41574-024-01057-w","article-title":"Polycystic ovary syndrome as a metabolic disease","volume":"21","author":"Helvaci","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.tem.2007.07.004","article-title":"Pathophysiology and types of dyslipidemia in PCOS","volume":"18","author":"Chrousos","year":"2007","journal-title":"Trends Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"4341","DOI":"10.3390\/nu14204341","article-title":"High-fat diet and female fertility across lifespan: a comparative lesson from mammal models","volume":"14","author":"Di Berardino","year":"2022","journal-title":"Nutrients"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1161\/CIRCULATIONAHA.123.065827","article-title":"Polycystic ovary syndrome fuels cardiovascular inflammation and aggravates ischemic cardiac injury","volume":"148","author":"Gao","year":"2023","journal-title":"Circulation"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.fertnstert.2010.12.027","article-title":"Lipid levels in polycystic ovary syndrome: systematic review and Meta-analysis","volume":"95","author":"Wild","year":"2011","journal-title":"Fertil Steril"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.jare.2024.10.038","article-title":"Genetic associations of metabolic factors and therapeutic drug targets with polycystic ovary syndrome","volume":"75","author":"Zhang","year":"2024","journal-title":"J Adv Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/1741-7015-10-153","article-title":"Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis","volume":"10","author":"Zhao","year":"2012","journal-title":"BMC Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1146\/annurev-physiol-032122-030352","article-title":"Fatty acid transport and signaling: mechanisms and physiological implications","volume":"85","author":"Samovski","year":"2023","journal-title":"Annu Rev Physiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/S2213-8587(22)00163-2","article-title":"Polycystic ovary syndrome","volume":"10","author":"Joham","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"101180","DOI":"10.1016\/j.plipres.2022.101180","article-title":"Very long chain fatty acids","volume":"87","author":"Kyselov\u00e1","year":"2022","journal-title":"Prog Lipid Res"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/s0968-0004(02)02168-0","article-title":"Polyunsaturated fatty acid synthesis: what will they think of next?","volume":"27","author":"Wallis","year":"2002","journal-title":"Trends Biochem Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1002\/cphy.c130024","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr Physiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"101257","DOI":"10.1016\/j.plipres.2023.101257","article-title":"Advances in research on microbial conjugated linoleic acid bioconversion","volume":"93","author":"Wu","year":"2024","journal-title":"Prog Lipid Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1038\/s41467-024-45782-2","article-title":"Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans","volume":"15","author":"Fox","year":"2024","journal-title":"Nat Commun"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.plipres.2013.12.001","article-title":"Regulation of energy metabolism by long-chain fatty acids","volume":"53","author":"Nakamura","year":"2014","journal-title":"Prog Lipid Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1021\/pr401130w","article-title":"Serum metabolomics study of polycystic ovary syndrome based on liquid chromatography-mass spectrometry","volume":"13","author":"Zhao","year":"2014","journal-title":"J Proteome Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"jc.2016-2692","DOI":"10.1210\/jc.2016-2692","article-title":"Discovery of novel lipid profiles in PCOS: do insulin and androgen oppositely regulate bioactive lipid production?","volume":"102","author":"Li","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1077590","DOI":"10.3389\/fendo.2023.1077590","article-title":"Serum fatty acid profiles associated with metabolic risk in women with polycystic ovary syndrome","volume":"14","author":"Tian","year":"2023","journal-title":"Front Endocrinol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jpba.2014.02.014","article-title":"Characterizing plasma phospholipid fatty acid profiles of polycystic ovary syndrome patients with and without insulin resistance using GC-MS and chemometrics approach","volume":"95","author":"Zhang","year":"2014","journal-title":"J Pharm Biomed Anal"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"109548","DOI":"10.1016\/j.jnutbio.2023.109548","article-title":"Metabolome implies increased fatty acid utilization and histone methylation in the follicles from hyperandrogenic PCOS women","volume":"125","author":"Xu","year":"2023","journal-title":"J Nutr Biochem"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1159\/000484325","article-title":"Saturated fat intake is related to heart rate variability in women with polycystic ovary syndrome","volume":"71","author":"Graff","year":"2017","journal-title":"Ann Nutr Metab"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"4683","DOI":"10.1007\/s00216-015-8670-x","article-title":"Serum metabolomics study of polycystic ovary syndrome based on UPLC-QTOF-MS coupled with a pattern recognition approach","volume":"407","author":"Dong","year":"2015","journal-title":"Anal Bioanal Chem"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"E707","DOI":"10.1152\/ajpendo.00532.2018","article-title":"Amino acid and fatty acid Metabolomic profile during fasting and hyperinsulinemia in girls with polycystic ovarian syndrome","volume":"316","author":"Cree-Green","year":"2019","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"960274","DOI":"10.3389\/fendo.2022.960274","article-title":"Follicular fluid Lipidomic profiling reveals potential biomarkers of polycystic ovary syndrome: A pilot study","volume":"13","author":"Ding","year":"2022","journal-title":"Front Endocrinol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"739","DOI":"10.3390\/biom12060739","article-title":"Myristic acid supplementation aggravates high fat diet-induced adipose inflammation and systemic insulin resistance in mice","volume":"12","author":"Saraswathi","year":"2022","journal-title":"Biomolecules"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"111862","DOI":"10.1016\/j.celrep.2022.111862","article-title":"Blocking AMPK \u03921 Myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis","volume":"41","author":"Neopane","year":"2022","journal-title":"Cell Rep"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jpba.2016.01.025","article-title":"UHPLC\/Q-TOFMS-based plasma metabolomics of polycystic ovary syndrome patients with and without insulin resistance","volume":"121","author":"Chen","year":"2016","journal-title":"J Pharm Biomed Anal"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"hoae002","DOI":"10.1093\/hropen\/hoae002","article-title":"Attenuation of palmitic acid-induced lysyl oxidase overexpression in the ovary contributes to the improvement of ovulation in obesity by metformin","volume":"2024","author":"Zhang","year":"2024","journal-title":"Hum Reprod Open"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1530\/JME-18-0214","article-title":"Palmitic acid causes insulin resistance in granulosa cells via activation of JNK","volume":"62","author":"Xu","year":"2019","journal-title":"J Mol Endocrinol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1210\/endo.142.8.8293","article-title":"Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells","volume":"142","author":"Mu","year":"2001","journal-title":"Endocrinology"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-023-43650-z","article-title":"Cyclical Palmitoylation regulates TLR9 Signalling and systemic autoimmunity in mice","volume":"15","author":"Ni","year":"2024","journal-title":"Nat Commun"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"100032","DOI":"10.1016\/j.clnves.2025.100032","article-title":"S-palmitoylation: a novel player in cancer and its emerging therapeutic implications","volume":"1","author":"Wang","year":"2025","journal-title":"Cell Investig"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s12958-021-00823-z","article-title":"TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids","volume":"19","author":"Wang","year":"2021","journal-title":"Reprod Biol Endocrinol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s13048-021-00934-6","article-title":"Gene Cascade analysis in human granulosa tumor cells (KGN) following exposure to high levels of free fatty acids and insulin","volume":"14","author":"Tremblay","year":"2021","journal-title":"J Ovarian Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/ajcn\/73.1.41","article-title":"Behenic acid is a cholesterol-raising saturated fatty acid in humans","volume":"73","author":"Cater","year":"2001","journal-title":"Am J Clin Nutr"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e633","DOI":"10.1210\/clinem\/dgad561","article-title":"Association of Circulating Very Long-Chain Saturated Fatty Acids with Cardiovascular Mortality in NHANES 2003-2004, 2011-2012","volume":"109","author":"Tao","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1016\/j.fertnstert.2014.08.018","article-title":"Elevated non-esterified fatty acid concentrations during in vitro murine follicle growth Alter follicular physiology and reduce oocyte developmental competence","volume":"102","author":"Valckx","year":"2014","journal-title":"Fertil Steril"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"737","DOI":"10.21451\/1984-3143-AR2018-0063","article-title":"Cumulus cells protect the oocyte against saturated free fatty acids","volume":"15","author":"Aardema","year":"2018","journal-title":"Anim Reprod"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"10245","DOI":"10.3390\/ijms231810245","article-title":"Lower plasmatic levels of saturated fatty acids and a characteristic fatty acid composition in the ovary could contribute to the high-fertility phenotype in Dummerstorf Superfertile mice","volume":"23","author":"Calanni-Pileri","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"115586","DOI":"10.1016\/j.biopha.2023.115586","article-title":"SCD1 is the critical signaling hub to mediate metabolic diseases: mechanism and the development of its inhibitors","volume":"170","author":"Sun","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1095\/biolreprod.116.146159","article-title":"Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress","volume":"96","author":"Aardema","year":"2017","journal-title":"Biol Reprod"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e13945","DOI":"10.7717\/peerj.13945","article-title":"Effects of CRISPR\/Cas9-mediated Stearoyl-coenzyme A desaturase 1 knockout on mouse embryo development and lipid synthesis","volume":"10","author":"Tian","year":"2022","journal-title":"PeerJ"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"330","DOI":"10.3390\/ijms22010330","article-title":"Monounsaturated fatty acids in obesity-related inflammation","volume":"22","author":"Ravaut","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"7312","DOI":"10.1021\/acs.jafc.2c08637","article-title":"Nobiletin ameliorates nonalcoholic fatty liver disease by regulating gut microbiota and Myristoleic acid metabolism","volume":"71","author":"Li","year":"2023","journal-title":"J Agric Food Chem"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1136\/gutjnl-2019-319114","article-title":"Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation","volume":"69","author":"Quan","year":"2020","journal-title":"Gut"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1373\/clinchem.2011.176396","article-title":"Metabolic heterogeneity in polycystic ovary syndrome is determined by obesity: plasma Metabolomic approach using GC-MS","volume":"58","author":"Escobar-Morreale","year":"2012","journal-title":"Clin Chem"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.cell.2008.07.048","article-title":"Identification of a Lipokine, a lipid hormone linking adipose tissue to systemic metabolism","volume":"134","author":"Cao","year":"2008","journal-title":"Cell"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41522-023-00415-2","article-title":"Alleviation of Limosilactobacillus Reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via Capric acid and GALR1 signaling","volume":"9","author":"Li","year":"2023","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0967199417000582","article-title":"Oleic acid in the modulation of oocyte and preimplantation embryo development","volume":"26","author":"Fayezi","year":"2018","journal-title":"Zygote"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1210\/clinem\/dgac281","article-title":"Elevated levels of follicular fatty acids induce ovarian inflammation via ERK1\/2 and inflammasome activation in PCOS","volume":"107","author":"Lai","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"3469","DOI":"10.3390\/jcm10163469","article-title":"Dietary and physical activity habits in adolescent girls with polycystic ovary syndrome (PCOS)-HAstudy","volume":"10","author":"Mizgier","year":"2021","journal-title":"J Clin Med"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/ejcn.2010.266","article-title":"Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS","volume":"65","author":"Kalgaonkar","year":"2011","journal-title":"Eur J Clin Nutr"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"101198","DOI":"10.1016\/j.plipres.2022.101198","article-title":"Endoplasmic reticulum stress and lipids in health and diseases","volume":"89","author":"Celik","year":"2023","journal-title":"Prog Lipid Res"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s13668-023-00451-6","article-title":"The effect on inflammation of adherence to the Mediterranean diet in polycystic ovary syndrome","volume":"12","author":"\u00c7\u0131tar Daz\u0131ro\u011flu","year":"2023","journal-title":"Curr Nutr Rep"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"21195","DOI":"10.1038\/srep21195","article-title":"FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome","volume":"6","author":"Tian","year":"2016","journal-title":"Sci Rep"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1039\/d0fo01976c","article-title":"The effects of low-ratio n-6\/n-3 PUFA on biomarkers of inflammation: A systematic review and Meta-analysis","volume":"12","author":"Wei","year":"2021","journal-title":"Food Funct"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1530\/REP-19-0136","article-title":"Elevated levels of arachidonic acid metabolites in follicular fluid of PCOS patients","volume":"159","author":"Li","year":"2020","journal-title":"Reproduction"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"865748","DOI":"10.3389\/fendo.2022.865748","article-title":"Arachidonic acid in follicular fluid of PCOS induces oxidative stress in a human ovarian granulosa tumor cell line (KGN) and upregulates GDF15 expression as a response","volume":"13","author":"Ma","year":"2022","journal-title":"Front Endocrinol"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1080\/21623945.2019.1710021","article-title":"Differences in fatty acid profiles and desaturation indices of abdominal subcutaneous adipose tissue between pregnant women with and without PCOS","volume":"9","author":"Emami","year":"2020","journal-title":"Adipocyte"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1111\/jcmm.13614","article-title":"Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats","volume":"22","author":"Huang","year":"2018","journal-title":"J Cell Mol Med"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.3390\/nu11102278","article-title":"Adherence to the Mediterranean diet, dietary patterns and body composition in women with polycystic ovary syndrome (PCOS)","volume":"11","author":"Barrea","year":"2019","journal-title":"Nutrients"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/REP-22-0023","article-title":"Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients","volume":"164","author":"Feng","year":"2022","journal-title":"Reproduction"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3390\/nu14010073","article-title":"Association of macronutrients composition, physical activity and serum androgen concentration in young women with polycystic ovary syndrome","volume":"14","author":"Mizgier","year":"2021","journal-title":"Nutrients"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1002\/ptr.7698","article-title":"The effects of flaxseed or its oil supplementations on polycystic ovary syndrome: a systematic review of clinical trials","volume":"37","author":"Emamat","year":"2023","journal-title":"Phytother Res"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1016943","DOI":"10.3389\/fnut.2022.1016943","article-title":"Associations between Omega-3 fatty acids and insulin resistance and body composition in women with polycystic ovary syndrome","volume":"9","author":"Lu","year":"2022","journal-title":"Front Nutr"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12958-018-0346-x","article-title":"Effectiveness of omega-3 fatty acid for polycystic ovary syndrome: a systematic review and meta-analysis","volume":"16","author":"Yang","year":"2018","journal-title":"Reprod Biol Endocrinol"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1017\/S0007114521003007","article-title":"Dietary and serum N-3 PUFA and polycystic ovary syndrome: a matched case-control study","volume":"128","author":"Lu","year":"2022","journal-title":"Br J Nutr"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"3842","DOI":"10.1210\/jc.2009-0870","article-title":"Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: A randomized controlled trial employing proton magnetic resonance spectroscopy","volume":"94","author":"Cussons","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13048-023-01130-4","article-title":"Effects of N-3 polyunsaturated fatty acid on metabolic status in women with polycystic ovary syndrome: A Meta-analysis of randomized controlled trials","volume":"16","author":"Zhou","year":"2023","journal-title":"J Ovarian Res"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1080\/07315724.2012.10720443","article-title":"Omega-3 fatty acids improve glucose metabolism without effects on obesity values and serum Visfatin levels in women with polycystic ovary syndrome","volume":"31","author":"Rafraf","year":"2012","journal-title":"J Am Coll Nutr"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/ajcn\/75.1.119","article-title":"Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells","volume":"75","author":"Toborek","year":"2002","journal-title":"Am J Clin Nutr"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"103345","DOI":"10.1016\/j.jri.2021.103345","article-title":"Increased pro-inflammatory cytokines in ovary and effect of \u03b3-linolenic acid on adipose tissue inflammation in a polycystic ovary syndrome model","volume":"146","author":"Prabhu","year":"2021","journal-title":"J Reprod Immunol"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.repbio.2020.05.004","article-title":"\u03b3-Linolenic acid ameliorates DHEA induced pro-inflammatory response in polycystic ovary syndrome via PPAR-\u03b3 signaling in rats","volume":"20","author":"Prabhu","year":"2020","journal-title":"Reprod Biol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"119456","DOI":"10.1016\/j.lfs.2021.119456","article-title":"The effect of \u03b3-linolenic acid on polycystic ovary syndrome associated focal segmental glomerulosclerosis via TGF-\u03b2 pathway","volume":"276","author":"D Prabhu","year":"2021","journal-title":"Life Sci"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.3390\/nu15081927","article-title":"N-3 PUFA promotes ferroptosis in PCOS GCs by inhibiting YAP1 through activation of the hippo pathway","volume":"15","author":"Zhang","year":"2023","journal-title":"Nutrients"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"hoae013","DOI":"10.1093\/hropen\/hoae013","article-title":"Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS","volume":"2024","author":"Li","year":"2024","journal-title":"Hum Reprod Open"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41467-023-44364-y","article-title":"Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use","volume":"15","author":"Worthmann","year":"2024","journal-title":"Nat Commun"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"64","DOI":"10.4103\/jrms.JRMS_644_16","article-title":"Omega-3 supplementation effects on polycystic ovary syndrome symptoms and metabolic syndrome","volume":"22","author":"Khani","year":"2017","journal-title":"J Res Med Sci"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1210\/jc.2003-030666","article-title":"Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome","volume":"89","author":"Kasim-Karakas","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"7397","DOI":"10.1039\/c9fo01730e","article-title":"Roles of different N-3\/n-6 PUFA ratios in ovarian cell development and steroidogenesis in PCOS rats","volume":"10","author":"Ma","year":"2019","journal-title":"Food Funct"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s13048-023-01162-w","article-title":"Effects of N-3 PUFA supplementation on oocyte in vitro maturation in mice with polycystic ovary syndrome","volume":"16","author":"Ma","year":"2023","journal-title":"J Ovarian Res"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3389\/fendo.2020.00284","article-title":"Dietary \u03b1-linolenic acid-rich flaxseed oil exerts beneficial effects on polycystic ovary syndrome through sex steroid hormones-microbiota-inflammation Axis in rats","volume":"11","author":"Wang","year":"2020","journal-title":"Front Endocrinol"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s13048-023-01227-w","article-title":"Effects of gut microbiota on Omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice","volume":"16","author":"Zhang","year":"2023","journal-title":"J Ovarian Res"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"110615","DOI":"10.1016\/j.mce.2019.110615","article-title":"High-fat diet-induced dysregulation of ovarian gene expression is restored with chronic Omega-3 fatty acid supplementation","volume":"499","author":"Hohos","year":"2020","journal-title":"Mol Cell Endocrinol"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1186\/s12967-020-02519-1","article-title":"Impact of different Omega-3 fatty acid sources on lipid, hormonal, blood glucose, weight gain and histopathological damages profile in PCOS rat model","volume":"18","author":"Komal","year":"2020","journal-title":"J Transl Med"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1152\/physrev.00041.2018","article-title":"Free fatty acid receptors in health and disease","volume":"100","author":"Kimura","year":"2020","journal-title":"Physiol Rev"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.cell.2020.07.027","article-title":"SnapShot: FABP functions","volume":"182","author":"Li","year":"2020","journal-title":"Cell"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s00011-017-1045-3","article-title":"Association of IL-1\u03b2, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome","volume":"66","author":"Rashid","year":"2017","journal-title":"Inflamm Res"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1007\/s00404-014-3422-2","article-title":"Associations between adipocyte fatty acid-binding protein and clinical parameters in polycystic ovary syndrome","volume":"291","author":"Do\u011fanay","year":"2015","journal-title":"Arch Gynecol Obstet"},{"key":"ref92","first-page":"3186","article-title":"Relations of serum adipocyte fatty acid binding protein to sex hormone and lipoproteins in patients with polycystic ovary syndrome","volume":"86","author":"Hu","year":"2006","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"935","DOI":"10.3109\/09513590.2011.569608","article-title":"Fatty acid-binding Protein-4 plasma levels are associated to metabolic abnormalities and response to therapy in girls and young women with androgen excess","volume":"27","author":"L\u00e1zaro","year":"2011","journal-title":"Gynecol Endocrinol"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1007\/s12020-011-9495-9","article-title":"Expression and regulation of adipocyte fatty acid binding protein in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome","volume":"40","author":"Hu","year":"2011","journal-title":"Endocrine"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s13148-020-00970-x","article-title":"Dynamic changes in chromatin accessibility, altered adipogenic gene expression, and total versus de novo fatty acid synthesis in subcutaneous adipose stem cells of normal-weight polycystic ovary syndrome (PCOS) women during adipogenesis: evidence of cellular programming","volume":"12","author":"Leung","year":"2020","journal-title":"Clin Epigenetics"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3109\/09513590.2013.774360","article-title":"Free fatty acid binding Protein-4 and retinol binding Protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies","volume":"29","author":"Karakas","year":"2013","journal-title":"Gynecol Endocrinol"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"107634","DOI":"10.1016\/j.ypmed.2023.107634","article-title":"FABP5 inhibitor SBFI-26 regulates FOXM1 expression and Wnt signaling pathway in ovarian granulosa cell of patients with polycystic ovary syndrome","volume":"174","author":"Cheng","year":"2023","journal-title":"Prev Med"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13048-024-01368-6","article-title":"High levels of fatty acid-binding protein 5 excessively enhances fatty acid synthesis and proliferation of granulosa cells in polycystic ovary syndrome","volume":"17","author":"Liu","year":"2024","journal-title":"J Ovarian Res"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"e99","DOI":"10.1038\/emm.2014.38","article-title":"CD36, a scavenger receptor implicated in atherosclerosis","volume":"46","author":"Park","year":"2014","journal-title":"Exp Mol Med"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1016\/j.cmet.2023.09.012","article-title":"CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression","volume":"35","author":"Terry","year":"2023","journal-title":"Cell Metab"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1093\/humrep\/dep122","article-title":"Omental adipose tissue overexpression of fatty acid transporter CD36 and decreased expression of hormone-sensitive lipase in insulin-resistant women with polycystic ovary syndrome","volume":"24","author":"Seow","year":"2009","journal-title":"Hum Reprod"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.3760\/cma.j.issn.0376-2491.2016.25.009","article-title":"Expression and regulation of CD36 mRNA in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome","volume":"96","author":"Hu","year":"2016","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1071\/RD18292","article-title":"CD36- and obesity-associated granulosa cells dysfunction","volume":"31","author":"Wu","year":"2019","journal-title":"Reprod Fertil Dev"},{"key":"ref104","first-page":"591","article-title":"Correlation between local hormones and CD36 transcription level in women with polycystic ovary","volume":"39","author":"Yao","year":"2004","journal-title":"Zhonghua Fu Chan Ke Za Zhi"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12020-015-0558-1","article-title":"Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome","volume":"50","author":"Tepav\u010devi\u0107","year":"2015","journal-title":"Endocrine"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"328","DOI":"10.2337\/dc07-1424","article-title":"Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment","volume":"31","author":"Glintborg","year":"2008","journal-title":"Diabetes Care"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.mam.2012.07.010","article-title":"SLC27 fatty acid transport proteins","volume":"34","author":"Anderson","year":"2013","journal-title":"Mol Asp Med"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1053\/j.gastro.2006.02.012","article-title":"Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity","volume":"130","author":"Hubbard","year":"2006","journal-title":"Gastroenterology"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"156054","DOI":"10.1016\/j.metabol.2024.156054","article-title":"Hepatocyte-specific SLC27A4 deletion ameliorates nonalcoholic fatty liver disease in mice via suppression of phosphatidylcholine-mediated PXR activation","volume":"162","author":"Shen","year":"2025","journal-title":"Metabolism"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1111\/bph.70334","article-title":"The role of free-fatty acid receptors FFA1 and FFA4 in organ fibrosis","volume":"183","author":"Karmokar","year":"2026","journal-title":"Br J Pharmacol"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"e2219569120","DOI":"10.1073\/pnas.2219569120","article-title":"Molecular mechanism of fatty acid activation of FFAR1","volume":"120","author":"Kumari","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"eadd6220","DOI":"10.1126\/science.add6220","article-title":"Unsaturated bond recognition leads to biased signal in a fatty acid receptor","volume":"380","author":"Mao","year":"2023","journal-title":"Science"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1017\/S0967199421000873","article-title":"GPR120 agonist ameliorated insulin resistance and improved ovarian function","volume":"30","author":"Liu","year":"2022","journal-title":"Zygote"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1507\/endocrj.EJ17-0102","article-title":"Effects of ovarian hormones on GPR120 mRNA expression in mouse pituitary Gonadotrophs","volume":"64","author":"Moriyama","year":"2017","journal-title":"Endocr J"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.ebiom.2018.12.019","article-title":"Protective role of GPR120 in the maintenance of pregnancy by promoting Decidualization via regulation of glucose metabolism","volume":"39","author":"Huang","year":"2019","journal-title":"EBioMedicine"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"101840","DOI":"10.1016\/j.molmet.2023.101840","article-title":"Hypothalamic free fatty acid receptor-1 regulates whole-body energy balance","volume":"79","author":"Dragano","year":"2023","journal-title":"Mol Metab"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"E30","DOI":"10.1152\/ajpendo.00257.2020","article-title":"GPR40 deficiency is associated with hepatic FAT\/CD36 upregulation, steatosis, inflammation, and cell injury in C57BL\/6 mice","volume":"320","author":"Lu","year":"2021","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"e29052","DOI":"10.1371\/journal.pone.0029052","article-title":"Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-Flutamide-metformin Polytherapy","volume":"6","author":"Vinaixa","year":"2011","journal-title":"PLoS One"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1797101\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:41:28Z","timestamp":1782898888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1797101\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":118,"alternative-id":["10.3389\/fnut.2026.1797101"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1797101","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1797101"}}