{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:06:56Z","timestamp":1791972416873,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K06757"],"award-info":[{"award-number":["19K06757"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17KK0188"],"award-info":[{"award-number":["17KK0188"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K07281"],"award-info":[{"award-number":["19K07281"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As glucose-dependent insulinotropic polypeptide (GIP) possesses pro-adipogenic action, the suppression of the GIP hypersecretion seen in obesity might represent a novel therapeutic approach to the treatment of obesity. However, the mechanism of GIP hypersecretion remains largely unknown. In the present study, we investigated GIP secretion in two mouse models of obesity: High-fat diet-induced obese (DIO) mice and leptin-deficient Lepob\/ob mice. In DIO mice, plasma GIP was increased along with an increase in GIP mRNA expression in the lower small intestine. Despite the robust alteration in the gut microbiome in DIO mice, co-administration of maltose and the \u03b1-glucosidase inhibitor (\u03b1-GI) miglitol induced the microbiome-mediated suppression of GIP secretion. The plasma GIP levels of Lepob\/ob mice were also elevated and were suppressed by fat transplantation. The GIP mRNA expression in fat tissue was not increased in Lepob\/ob mice, while the expression of an interleukin-1 receptor antagonist (IL-1Ra) was increased. Fat transplantation suppressed the expression of IL-1Ra. The plasma IL-1Ra levels were positively correlated with the plasma GIP levels. Accordingly, although circulating GIP levels are increased in both DIO and Lepob\/ob mice, the underlying mechanisms differ, and the anti-obesity actions of \u03b1-GIs and leptin sensitizers may be mediated partly by the suppression of GIP secretion.<\/jats:p>","DOI":"10.3390\/ijms20184448","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T10:52:26Z","timestamp":1568112746000},"page":"4448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diet-Induced Obese Mice and Leptin-Deficient Lepob\/ob Mice Exhibit Increased Circulating GIP Levels Produced by Different Mechanisms"],"prefix":"10.3390","volume":"20","author":[{"given":"Eunyoung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan"},{"name":"Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Miedzybrodzka","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6833-829X","authenticated-orcid":false,"given":"Ryo","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junki","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu 183-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu 183-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Immunology and Genomics, Osaka City University School of Medicine, Osaka 545-8585, Japan"},{"name":"Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Genomics, Osaka City University School of Medicine, Osaka 545-8585, Japan"},{"name":"Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Rodriguez-Cuenca","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vidal-Puig","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M.","family":"Gribble","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Reimann","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, 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