{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:39:58Z","timestamp":1790102398959,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Obesity is characterized by chronic low-grade inflammation, largely driven by macrophage infiltration into adipose tissue, which contributes to the development of insulin resistance. All-trans retinoic acid (ATRA), a biologically active metabolite of vitamin A, has demonstrated anti-inflammatory properties. This study examined the effects of ATRA on inflammation and insulin resistance using a coculture model comprising hypertrophied 3T3-L1 adipocytes and RAW264.7 macrophages. Coculture markedly elevated the production of pro-inflammatory mediators\u2014including nitric oxide, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interleukin-6\u2014and increased free fatty acid release while suppressing the secretion of anti-inflammatory adiponectin. Treatment with ATRA (0.1, 1, and 10 \u03bcM) significantly reversed these coculture-induced alterations (p &lt; 0.001). ATRA also inhibited the nuclear translocation of NF-\u03baB and downregulated the expression of retinol-binding protein 4 (RBP4). Moreover, ATRA improved insulin-stimulated glucose uptake in adipocytes rendered insulin-resistant by coculture (p &lt; 0.01), an effect associated with the restoration of glucose transporter 4 (GLUT4) and insulin receptor substrate-2 (IRS-2) expression. These findings suggest that ATRA effectively mitigates inflammation and insulin resistance arising from adipocyte\u2013macrophage interactions, highlighting its potential as a therapeutic agent for obesity-related metabolic disorders.<\/jats:p>","DOI":"10.3390\/molecules30204111","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T07:33:50Z","timestamp":1760686430000},"page":"4111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["All-Trans Retinoic Acid Attenuates Inflammation and Insulin Resistance Induced by Adipocyte\u2013Macrophage Coculture"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8148-2416","authenticated-orcid":false,"given":"Kwang-Rim","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Food Science & Nutrition, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-1709","authenticated-orcid":false,"given":"Hye-Kyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Science & Nutrition, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI92035","article-title":"Inflammatory mechanisms linking obesity and metabolic disease","volume":"127","author":"Saltiel","year":"2017","journal-title":"J. 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