{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:46:32Z","timestamp":1782978392693,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0210111"],"award-info":[{"award-number":["JP20ek0210111"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","award":["21\u2010092"],"award-info":[{"award-number":["21\u2010092"]}],"id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06276"],"award-info":[{"award-number":["16H06276"]}],"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":["22H04922"],"award-info":[{"award-number":["22H04922"]}],"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":["23K16764"],"award-info":[{"award-number":["23K16764"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intramuscular adipose tissue (IMAT) formation derived from muscle fibro\u2010adipogenic progenitors (FAPs) has been recognized as a pathological feature of sarcopenia. This study aimed to explore whether genetic and pharmacological gastric inhibitory polypeptide (GIP) receptor antagonism suppresses IMAT accumulation and ameliorates sarcopenia in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole body composition, grip strength, skeletal muscle weight, tibialis anterior (TA) muscle fibre cross\u2010sectional area (CSA) and TA muscle IMAT area were measured in young and aged male C57BL\/6 strain GIP receptor (<jats:italic>Gipr<\/jats:italic>)\u2010knockout (<jats:italic>Gipr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type (<jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup>) mice. FAPs isolated from lower limb muscles of 12\u2010week\u2010old <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice were cultured with GIP, and their differentiation into mature adipocytes was examined. Furthermore, TA muscle IMAT area and fibre CSA were measured in untreated <jats:italic>Gipr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice and GIP receptor antagonist\u2010treated <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice after glycerol injection into the TA muscles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Body composition analysis revealed that 104\u2010week\u2010old <jats:italic>Gipr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice had a greater proportion of lean tissue mass (73.7\u00a0\u00b1\u00a01.2% vs. 66.5\u00a0\u00b1\u00a02.7%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 vs. 104\u2010week\u2010old <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice) and less adipose tissue mass (13.1\u00a0\u00b1\u00a01.3% vs. 19.4\u00a0\u00b1\u00a02.6%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 vs. 104\u2010week\u2010old <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice). Eighty\u2010four\u2010week\u2010old <jats:italic>Gipr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited increases in grip strength (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), weights of TA (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), soleus (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), gastrocnemius (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and quadriceps femoris (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) muscles, and average TA muscle fibre CSA (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) along with a reduction in TA muscle IMAT area assessed by the number of perilipin\u2010positive cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) compared with 84\u2010week\u2010old <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice. Oil Red O staining analysis revealed 1.6\u2010 and 1.7\u2010fold increased adipogenesis in muscle FAPs cultured with 10 and 100\u00a0nM of GIP (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 vs. 0\u00a0nM of GIP, respectively). Furthermore, both untreated <jats:italic>Gipr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice and GIP receptor antagonist\u2010treated <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice for 14\u00a0days after glycerol injection into the TA muscles at 12\u00a0weeks of age showed reduced TA muscle IMAT area (1.39\u00a0\u00b1\u00a00.38% and 2.65\u00a0\u00b1\u00a00.36% vs. 6.54\u00a0\u00b1\u00a01.30%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 vs. untreated <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice, respectively) and increased average TA muscle fibre CSA (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 vs. untreated <jats:italic>Gipr<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GIP promotes the differentiation of muscle FAPs into adipocytes and its receptor antagonism suppresses IMAT accumulation and promotes muscle regeneration. Pharmacological GIP receptor antagonism may serve as a novel therapeutic approach for sarcopenia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13346","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T06:30:20Z","timestamp":1698474620000},"page":"2703-2718","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Gastric inhibitory polypeptide receptor antagonism suppresses intramuscular adipose tissue accumulation and ameliorates sarcopenia"],"prefix":"10.1002","volume":"14","author":[{"given":"Yuya","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Metabolism and Endocrinology Akita University Graduate School of Medicine  Akita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-605X","authenticated-orcid":false,"given":"Hiroki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department 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