{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:12:11Z","timestamp":1787069531801,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008644","name":"Japan Diabetes Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008644","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013489","name":"Yakult Bio-Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013489","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012627","name":"Japan Diabetes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012627","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K11758"],"award-info":[{"award-number":["22K11758"]}],"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":["23K16823"],"award-info":[{"award-number":["23K16823"]}],"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":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Overeating and inactivity are associated with type 2 diabetes. This study aimed to investigate its pathological basis using integrated omics and\n                      <jats:italic>db\/db\/m<\/jats:italic>\n                      ice, a model representing this condition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study involved housing 8\u2010week\u2010old\n                      <jats:italic>db\/m<\/jats:italic>\n                      and\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice for 8\u00a0weeks. Various analyses were conducted, including gene expression in skeletal muscle and small intestine using next\u2010generation sequencing; cytokine arrays of serum; assessment of metabolites in skeletal muscle, stool, and serum; and analysis of the gut microbiota. Histone modifications in small intestinal epithelial cells were profiled using CUT&amp;Tag.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with\n                      <jats:italic>db\/m<\/jats:italic>\n                      mice,\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice had 22.4% lower grip strength and approximately five times the visceral fat weight (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Serum cytokine arrays showed a 2.8\u2010fold relative concentration of VEGF\u2010A in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) and lower concentrations of several other cytokines. mRNA sequencing revealed downregulation of\n                      <jats:italic>Myh<\/jats:italic>\n                      expression in skeletal muscle, upregulation of lipid and glucose transporters, and downregulation of amino acid transporters in the small intestine of\n                      <jats:italic>db\/db\/m<\/jats:italic>\n                      ice. The concentrations of saturated fatty acids in skeletal muscle were significantly higher, and the levels of essential amino acids were lower in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice. Analysis of the gut microbiota, 16S rRNA sequencing, revealed lower levels of the phylum Bacteroidetes (59.7% vs. 44.9%) and higher levels of the phylum Firmicutes (20.9% vs. 31.4%) in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.003). The integrated signal of histone modifications of lipid and glucose transporters was higher, while the integrated signal of histone modifications of amino acid transporters was lower in the\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The multi\u2010omics approach provided insights into the epigenomic alterations in the small intestine, suggesting their involvement in the pathogenesis of inactivity\u2010induced muscle atrophy in obese mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13550","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T06:10:19Z","timestamp":1720851019000},"page":"2030-2045","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A multi\u2010omics approach to overeating and inactivity\u2010induced muscle atrophy in\n                    <i>db\/db<\/i>\n                    mice"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-1697","authenticated-orcid":false,"given":"Takuro","family":"Okamura","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"},{"name":"Department of Diabetes and Endocrinology Kyoto Okamoto Memorial Hospital  Kuze Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Senmaru","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Sasano","sequence":"additional","affiliation":[{"name":"AiSTI Science Co., Ltd.  Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31138-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S302"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13076"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13245"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e02611"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3484"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.11.001"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2025"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115558"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121964"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20180482"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ20-0564"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-022-00685-1"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030247"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.13951"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.162615"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15112580"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12814"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9488"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601554"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2534"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18262-6"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504978102"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241214"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01379"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00117504"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.8.5015"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01653"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00310.2019"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44270"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T22:46:56Z","timestamp":1727909216000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,13]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/jcsm.13550"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13550","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,13]]},"assertion":[{"value":"2023-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}