{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:49:22Z","timestamp":1791449362343,"version":"4.3.3"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The role of adenosine receptor 3 (AR3) signaling in adipogenesis remains unclear. Here, we show that AR3 antagonism by MRS1220 inhibited adipogenic differentiation in both C3H10T1\/2 and 3T3\u2010L1 cells, as evidenced by reduced lipid accumulation in both models and suppressed PPAR\u03b32 expression in C3H10T1\/2 cells. Transcriptomic profiling and pathway analysis performed in C3H10T1\/2 cells suggested that the\n                    <jats:italic>Ereg<\/jats:italic>\n                    gene, which encodes epiregulin (EREG), is a potential target of MRS1220 mediated adipogenesis inhibition. Mechanistically, MRS1220 induced EREG expression, leading to EGFR activation and leptin upregulation, which were critical for its anti\u2010adipogenic effect. Recombinant EREG mimicked, and EREG neutralization reversed, MRS1220's inhibitory activity. EGFR inhibition abolished MRS1220\u2010induced leptin expression and restored adipogenesis. Notably, AR3 knockdown abrogated MRS1220's effects on EREG induction, EGFR phosphorylation, leptin induction, and lipid accumulation. In contrast, the AR3 agonist CF101 enhanced adipogenesis independent of the EREG\u2010EGFR\u2010leptin axis. These findings establish AR3 as a key regulator of adipogenic differentiation and uncover an AR3\u2010EREG\u2010EGFR\u2010leptin signaling cascade as a mechanism by which AR3 antagonism inhibits adipogenesis. Targeting AR3 may offer a novel strategy to modulate adipose tissue formation in metabolic diseases.\n                  <\/jats:p>","DOI":"10.1002\/biof.70140","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:29:02Z","timestamp":1785724142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adenosine Receptor 3 Antagonism Suppresses Adipogenesis via the\n                    <scp>EREG<\/scp>\n                    \u2010\n                    <scp>EGFR<\/scp>\n                    \u2010Leptin Axis in Multipotent Cells"],"prefix":"10.1002","volume":"52","author":[{"given":"Chia\u2010Huei","family":"Lee","sequence":"first","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes  Miaoli 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