{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:18:02Z","timestamp":1788909482692,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) is frequently associated with cachexia, leading to poor prognoses and reduced quality of life. However, the mechanisms underlying adipose tissue atrophy, its pathological significance and its interaction with skeletal muscle remain poorly understood. We hypothesised that adipose tissue atrophy precedes muscle wasting in COPD\u2010associated cachexia, and muscle atrophy progresses through adipose\u2013muscle crosstalk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed chest computed tomography scans of 185 patients with COPD to quantify the cross\u2010sectional areas of the pectoralis muscle (PM), subcutaneous adipose tissue (SAT) and epicardial adipose tissue (EAT), and the percentage of low attenuation area (LAA%) as an index of emphysema. To elucidate the pathophysiological mechanisms underlying cachexia in COPD, we performed histological and molecular analyses of the lung, muscle and adipose tissues over time in a cigarette smoke\u2013induced emphysema mouse model. Further, we used an in\u00a0vitro culture system of differentiated adipocytes (3T3\u2010L1) and myotubes (C2C12) to study the effects of cigarette smoke extract (CSE) on adipose\u2013muscle interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In patients with COPD, the areas of PM, SAT and EAT all demonstrated significant negative correlations with LAA%; notably, PM and EAT were independently associated with the extent of emphysematous changes. In the smoke\u2010exposed murine model, adipose tissue atrophy was observed after 1\u2009month of exposure, accompanied by increased expressions of IL\u20106 and IL\u20101\u03b2, macrophage infiltration and the upregulation of the lipolytic enzymes ATGL and HSL. The adipose atrophy had further progressed after 3\u2009months of exposure, and the high expression of UCP1 was sustained, which suggested the browning of adipose tissue. Conversely, muscle atrophy was not evident at 1\u2009month but became apparent after 3\u2009months, coinciding with emphysema development. This was associated with the downregulation of the myogenic markers MyoD and Myogenin and the upregulation of the muscle degradation marker Atrogin\u20101. In\u00a0vitro experiments revealed that CSE exposure reduced lipid droplet content and induced IL\u20106 and IL\u20101\u03b2 expressions in adipocytes. Conditioned media from CSE\u2010treated adipocytes triggered myotube atrophy and downregulated MyoD and Myogenin but upregulated Atrogin\u20101.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that cigarette smoke\u2010induced adipose tissue atrophy precedes muscle wasting, and alterations in adipose tissue may contribute to muscle atrophy progression. Adipose tissue dysfunction may be implicated in the development of cachexia in patients with COPD, highlighting its potential as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70154","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T23:51:07Z","timestamp":1765324267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Adipose\u2013Muscle Crosstalk in COPD Cachexia: Early Adipose Atrophy Drives Subsequent Muscle Wasting"],"prefix":"10.1002","volume":"16","author":[{"given":"Takashi","family":"Shimada","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5046-3762","authenticated-orcid":false,"given":"Shotaro","family":"Chubachi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Arai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Otake","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Japan Community Health Care Organization (JCHO) Saitama Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Maetani","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Masaki","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kabata","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Miyata","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitake","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Radiology Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Jinzaki","sequence":"additional","affiliation":[{"name":"Department of Radiology Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Saitama Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Tokai University School of Medicine  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00214-2017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.597675"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000353211"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2023.107346"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000529031"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201307-229OC"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-023-02535-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2003.03898.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23151"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201410-1830PP"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11182893"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.10.006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101612"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01950-w"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.14712\/23362936.2015.49"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13721"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-019-1047-5"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202101-044OC"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201507-446OC"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148794"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0319"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21013"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00074.2015"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00128008"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42845"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/173498"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00460.2012"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.028"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.276733.115"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.06.011"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2003"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0449OC"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26811"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198973"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.111.023499"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12070"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2010.05.008"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.4.7551381"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.10.047"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201610-821OC"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:41:25Z","timestamp":1772959285000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jcsm.70154"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70154","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70154"}}