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In this review, we first comprehensively describe six major lipokines, including palmitoleic acid (C16:1n7), 12,13\u2010dihydroxy\u20109Z\u2010octadecenoic acid (12,13\u2010diHOME), fatty acid esters of hydroxy fatty acids (FAHFAs), 12\u2010hydroxyeicosapentaenoic acid (12\u2010HEPE), lysophosphatidic acid (LPA), and 15\u2010hydroxyeicosatetraenoic acid (15\u2010HETE), focusing on their mechanistic roles in energy metabolism and inflammatory modulation as well as their cross\u2010talk within different signaling pathways. These lipokines collectively contribute to metabolic homeostasis by regulating multiple pathways, including insulin signaling, AMPK activation, inflammatory modulation, and G\u2010protein\u2010coupled receptor\u2010mediated pathways. Furthermore, we clarify the associations between lipokines and various diseases such as obesity, type 2 diabetes, cardiovascular diseases, non\u2010alcoholic fatty liver disease, inflammatory disorders, and cancer, and discuss their potential as biomarkers and therapeutic targets. Despite current challenges, including functional complexity, limitations of model systems, and difficulties in clinical translation, lipokines demonstrate promising prospects in the prevention and treatment of metabolic diseases and application in precision medicine. Future research should prioritize the elucidation of the specific action mechanisms of different lipokines, development of highly sensitive detection methodologies, and large\u2010scale clinical trials to facilitate the translation of the research results into practical medical applications.<\/jats:p>","DOI":"10.1002\/cph4.70072","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T05:44:27Z","timestamp":1763185467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Roles of Diverse Lipokines in Metabolic Homeostasis and Their Associations With Various Diseases"],"prefix":"10.1002","volume":"15","author":[{"given":"Chenxuan","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxing","family":"Song","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Huazhong Agricultural University  Wuhan China"},{"name":"Frontiers Science Center for Animal Breeding and Sustainable Production  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0305\u20104179(82)90129\u20102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394\u2010020\u201002391\u20101"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2005.03.003"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312695"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.08.001"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476\u2010511x\u201013\u2010199"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/hmbci\u20102015\u20100073"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2020.101053"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020999118"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.048"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098\u2010023\u201001115\u20109"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010004\u20101609\u2010y"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.192"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.646992"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11373\u2010007\u20109223\u2010x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010017\u20103896\u2010y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.08.019"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2017.1321710"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425915576345"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.2a0918\u2010368rr"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.08.004"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12030446"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009741"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/futurepharmacol4010014"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M082008"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113892010340506241014112341"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18779"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2011.02.001"},{"key":"e_1_2_11_31_1","first-page":"3194","article-title":"Lysophosphatidic Acid Promotes Matrix Metalloproteinase (MMP) Activation and MMP\u2010Dependent Invasion in Ovarian Cancer Cells","volume":"61","author":"Fishman D. 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