{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:33:29Z","timestamp":1791408809083,"version":"4.3.3"},"reference-count":23,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Council MOST","award":["NSTC 113-2314-B-A49-069"],"award-info":[{"award-number":["NSTC 113-2314-B-A49-069"]}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["KSVGH111-120"],"award-info":[{"award-number":["KSVGH111-120"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["KSVGH115-068"],"award-info":[{"award-number":["KSVGH115-068"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zuoying Armed Forces General Hospital","award":["ZYAFGH_A_114025"],"award-info":[{"award-number":["ZYAFGH_A_114025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myeloid differentiation factor 88 (MyD88) signaling plays a central role in inflammatory pathway activation. Adipose-derived interleukin-10 (IL-10), which is induced by insulin and lipopolysaccharides, suppresses hepatic glucose production. This study investigated the role of MyD88\/IL-10 signaling in diabetes-induced systemic inflammation and hepatic gluconeogenesis. Stromal vascular fractions (SVFs) were isolated from the adipose tissue of Leprdb\/db and Leprdb\/dbMyD88\u2212\/\u2212 mice and treated with IL-10 followed by analysis of inflammatory cytokine expression. IL-10 (10 or 50 ng) was injected into adipose tissue of type 2 DM (T2DM) (Leprdb\/db) mice to investigate its effect on blood dipeptidyl peptidase-4 (DPP4) activity, insulin resistance, and hepatic gluconeogenic signaling. Hepatic inflammatory markers, gluconeogenic gene expression, and metabolic parameters were assessed. Compared with wild-type mice, Leprdb\/db mice exhibited significantly reduced FOXP3 protein expression and IL-10 levels in adipose tissue, accompanied by increased blood DPP4 activity and adiponectin levels, elevated hepatic inflammatory cytokines, and increased G6pc and Pck1 mRNA expression. In contrast, Leprdb\/dbMyD88\u2212\/\u2212 mice showed increased Foxp3 protein and PDGF\u03b1 mRNA expression, decreased IL-6 and CCL2 mRNA expression in SVFs, increased IL-10 levels in adipose tissue, and lower blood adiponectin and ALT levels. MyD88 deletion also attenuated Kupffer cell accumulation, hepatic inflammatory cytokine expression, and gluconeogenic gene expression. In vitro, IL-10 treatment of SVFs from Leprdb\/db mice significantly reduced IL-6 and CCL2 expression and increased Foxp3 mRNA expression. In vivo, adipose IL-10 injection increased Foxp3 and IL-10 expression, expanded Treg cells in SVFs, and activated hepatic Akt signaling, while suppressing pJNK and pNF-\u03baB signaling. These changes were accompanied by reduced blood DPP4 activity, ALT and adiponectin levels, decreased Kupffer cell-derived inflammatory cytokines, reduced hepatic G6pc and Pck1 expression, and improved glucose tolerance. MyD88 signaling induces adipose IL-6 and CCL2, liver inflammation and gluconeogenesis, and blood DPP4 activity by reducing IL-10 and Foxp3 of adipose tissue in T2DM. Enhancing adipose IL-10 induces Treg expansion, inhibits JNK and NF-\u03baB signaling, and alleviates hepatic gluconeogenesis and insulin resistance. MyD88 inhibition or IL-10 elevation in adipose tissue may represent a novel strategy for metabolic syndrome.<\/jats:p>","DOI":"10.3390\/ijms27062883","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"2883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MyD88 Inhibition Ameliorates Diabetes-Induced Hepatic Inflammation and Gluconeogenesis Through Adipose IL-10 Induction"],"prefix":"10.3390","volume":"27","author":[{"given":"Yi-Cheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Surgery, Zuoying Armed Forces General Hospital, Kaohsiung 81342, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Chi","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Veterans General Hospital, No.386, Ta-Chung 1st Road, Kaohsiung 81362, Taiwan"},{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, No.20, Weixin Road, Pingtung 90741, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hsuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Veterans General Hospital, No.386, Ta-Chung 1st Road, Kaohsiung 81362, Taiwan"},{"name":"Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hua","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Veterans General Hospital, No.386, Ta-Chung 1st Road, Kaohsiung 81362, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-1248","authenticated-orcid":false,"given":"Lee-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Veterans General Hospital, No.386, Ta-Chung 1st Road, Kaohsiung 81362, Taiwan"},{"name":"Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei 11221, Taiwan"},{"name":"Department of Biological Sciences, National Sun Yat-Sen University, No.70, Lien-Hai Road, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molcel.2020.06.016","article-title":"Fed Macrophages Hit the Liver\u2019s Sweet Spot with IL-10","volume":"79","author":"Sulen","year":"2020","journal-title":"Mol. 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