{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:16:38Z","timestamp":1769793398064,"version":"3.49.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Allograft inflammatory factor-1 (AIF-1), a cytokine secreted by activated monocytes, macrophages, and lymphocytes, has emerged as a critical regulator of pathological processes spanning renal diseases, rheumatoid arthritis, cancer, cardiovascular disorders, neurological pathologies, and transplant-related conditions. Population-based studies have associated sequence variants near the AIF-1 locus with obesity, though AIF-1\u2019s potential pathophysiological involvement remains uninvestigated. Understanding its molecular characteristics, receptor interactions, and signaling pathways is essential for elucidating its biological functions. This review comprehensively examines AIF-1\u2019s involvement in inflammatory and metabolic pathogenesis, particularly focusing on obesity and inflammation. Through systematic literature analysis, we consolidated current knowledge on AIF-1\u2019s functions and analyzed studies exploring its roles in obesity, insulin resistance, and inflammation to clarify broader disease mechanisms. AIF-1 exerts pleiotropic effects on immune cells, insulin signaling, and adipocytes. Elevated AIF-1 levels correlate with inflammatory adipocytes and obesity, while reduced AIF-1 promotes weight loss through regulation of monoamine oxidase A and decreased leptin\/resistin production. Deciphering AIF-1\u2019s complex roles in inflammation and metabolic disorders offers critical insights for therapeutic development. Targeting AIF-1 or AIF1-like (AIF1L) may yield novel strategies to mitigate disease progression and enhance clinical management of obesity.<\/jats:p>","DOI":"10.3389\/fendo.2026.1735573","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:26:57Z","timestamp":1769750817000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The multifaceted role of AIF-1 in metabolic dysregulation: bridging inflammation, insulin resistance, and obesity"],"prefix":"10.3389","volume":"17","author":[{"given":"Jie","family":"Huang","sequence":"first","affiliation":[{"name":"School of Medicine, Hangzhou City University","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Anji People\u2019s Hospital, Affiliated Anji Hospital, School of Medicine, Hangzhou City University","place":["Huzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Hangzhou City University","place":["Hangzhou, China"]},{"name":"Anji People\u2019s Hospital, Affiliated Anji Hospital, School of Medicine, Hangzhou City University","place":["Huzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2019.12.002","article-title":"Role of allograft inflammatory factor-1 in pathogenesis of diseases","volume":"218","author":"Sikora","year":"2020","journal-title":"Immunol Lett"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118003","article-title":"Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic 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