{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:49:57Z","timestamp":1792511397882,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Dipeptidyl peptidase\u20104 (DPP\u20104) inhibitors suppress the inactivation of incretin hormones and lower blood glucose levels by inhibiting DPP\u20104 function. Sodium\u2010glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels in an insulin\u2010independent manner by inhibiting renal reabsorption of glucose. DPP\u20104 and SGLT2 inhibitors each have the potential to improve hepatic steatosis; however, their combined effects remain unclear. In this study, we examined the effects of the combination of these drugs on hepatic steatosis using high\u2010fat diet\u2010fed mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>C57BL\/6J male mice were fed a 60% high\u2010fat diet for 2\u2009months to induce hepatic steatosis. Mice were divided into four groups (control; DPP\u20104 inhibitor anagliptin; SGLT2 inhibitor luseogliflozin; anagliptin and luseogliflozin combination), and the effects of each drug and their combination on hepatic steatosis after a 4\u2010week intervention were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were no differences in blood glucose levels among the four groups. Anagliptin suppresses inflammation\u2010 and chemokine\u2010related gene expression. It also improved macrophage fractionation in the liver. Luseogliflozin reduced body weight, hepatic gluconeogenesis and blood glucose levels in the oral glucose tolerance test. The combination treatment improved hepatic steatosis without interfering with the effects of anagliptin and luseogliflozin, respectively, and fat content and inflammatory gene expression in the liver were significantly improved in the combination group compared with the other groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination therapy with the DPP\u20104 inhibitor anagliptin and the SGLT2 inhibitor luseogliflozin inhibits fat deposition in the liver via anti\u2010inflammatory effects during the early phase of diet\u2010induced liver steatosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15548","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:18:20Z","timestamp":1710893900000},"page":"2339-2348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dipeptidyl peptidase\u20104 inhibitor and sodium\u2010glucose cotransporter 2 inhibitor additively ameliorate hepatic steatosis through different mechanisms of action in high\u2010fat diet\u2010fed mice"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8162-359X","authenticated-orcid":false,"given":"Yuichiro","family":"Iwamoto","sequence":"first","affiliation":[{"name":"Department of Diabetes, Metabolism and Endocrinology Kawasaki Medical School  Kurashiki 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