{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:00Z","timestamp":1792788780176,"version":"4.5.0"},"reference-count":0,"publisher":"American Diabetes Association","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"the Shanghai Rising-Star Program","award":["23QA1407400"],"award-info":[{"award-number":["23QA1407400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200941"],"award-info":[{"award-number":["82200941"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82325010"],"award-info":[{"award-number":["82325010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370879"],"award-info":[{"award-number":["82370879"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570944"],"award-info":[{"award-number":["82570944"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basic Research Project of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","award":["ynqn202207"],"award-info":[{"award-number":["ynqn202207"]}],"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Key Clinical Specialty","award":["Z155080000004"],"award-info":[{"award-number":["Z155080000004"]}]},{"name":"Shanghai Research Center for Endocrine and Metabolic Diseases","award":["2022ZZ01002"],"award-info":[{"award-number":["2022ZZ01002"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2025ZD0549400"],"award-info":[{"award-number":["2025ZD0549400"]}]},{"name":"Shanghai 2022 High Level Expert Support Special Foundation","award":["22YS1400500"],"award-info":[{"award-number":["22YS1400500"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Skeletal muscle plays a pivotal role in maintaining metabolic homeostasis by acting as a primary site for glucose disposal and insulin-mediated energy use. Here, through RNA sequencing of skeletal muscle from individuals with normal weight versus obesity, we identified that the extracellular matrix\u2013related gene dermatopontin (DPT) was significantly upregulated in the individuals with obesity. By establishing muscle-specific overexpression, knockdown, and knockout Dpt mouse models, we demonstrated that DPT ameliorated metabolic dysfunction by improving muscular mitochondrial function and exercise capacity, systemic insulin sensitivity, and glucose tolerance while reducing hepatic steatosis, suppressing appetite, and synergistically boosting energy expenditure under high-fat-diet feeding. Mechanistically, DPT activated a compensatory increase in the PERK\/eIF2\u03b1\/ATF4 endoplasmic reticulum stress pathway, leading to the transcriptional upregulation of growth differentiation factor (GDF) 15 expression and secretion. Importantly, the metabolic benefits of DPT were abolished in Gdf15\u2212\/\u2212 mice. Collectively, our study identified DPT as a novel, compensatorily expressed regulator in muscle during obesity, highlighting its potential as a therapeutic target for treating metabolic disorders.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>We identified dermatopontin (DPT) as a previously unrecognized compensatory regulator that is upregulated in skeletal muscle in obesity and preserves muscle function and systemic metabolic homeostasis, offering a potential therapeutic target for metabolic disorders. Mechanistically, DPT activates an adaptive PERK\/eIF2\u03b1\/ATF4 endoplasmic reticulum stress axis specifically under metabolic stress, but not under normal conditions, which enhances muscle function and directly counteracts metabolic deterioration, revealing a protective signaling cascade. This DPT-driven endoplasmic reticulum stress axis transcriptionally upregulates growth differentiation factor (GDF) 15 expression and secretion in muscle. Muscle-derived GDF15 exerts both local muscle-autonomous and systemic protective effects, uncovering a previously unrecognized muscle-to-organ cross-talk axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-0082","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:09:32Z","timestamp":1791994172000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Skeletal Muscle DPT Ameliorates Obesity and Metabolic Dysfunction via the PERK\/eIF2\u03b1\/ATF4-GDF15 Axis"],"prefix":"10.2337","author":[{"given":"Lingxin","family":"You","sequence":"first","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xu","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wen","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Yao","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baocheng","family":"Wan","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtian","family":"Yu","sequence":"additional","affiliation":[{"name":"2Clinical Research Center, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-6270","authenticated-orcid":false,"given":"Jing","family":"Yan","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4314-2386","authenticated-orcid":false,"given":"Cheng","family":"Hu","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"3Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,10,14]]},"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db26-0082\/898707\/db260082.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db26-0082\/898707\/db260082.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:09:33Z","timestamp":1791994173000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/doi\/10.2337\/db26-0082\/172812\/Skeletal-Muscle-DPT-Ameliorates-Obesity-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/db26-0082","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"article-number":"db260082"}}