{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:14:42Z","timestamp":1785420882204,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371220"],"award-info":[{"award-number":["32371220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32371220"],"award-info":[{"award-number":["32371220"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003347","name":"Fudan University","doi-asserted-by":"publisher","award":["BXH"],"award-info":[{"award-number":["BXH"]}],"id":[{"id":"10.13039\/501100003347","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BXH"],"award-info":[{"award-number":["BXH"]}],"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFMK"],"abstract":"<jats:p>Objectives: Circadian rhythms regulate key physiological processes, including metabolism and energy balance. Emerging evidence suggests that the timing of physical activity may influence metabolic outcomes. However, how the timing of endurance exercise impacts long-term metabolic health and the role of the circadian clock in this process remain unclear. This study aimed to investigate whether time-dependent endurance exercise improves metabolic health via circadian rhythm regulation. Methods: A 12-week endurance exercise protocol was established using wild-type (WT) and circadian-disrupted Clock\u039419 mice. Mice were assigned to exercise at Zeitgeber time 0 (ZT0) or Zeitgeber time 0 (ZT12), or to sedentary controls. Assessments included rotarod fatigue test, body weight, epididymal fat ratio, fasting blood glucose, serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-esterified fatty acids (NEFA), intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT). Results: Clock\u039419 mice exhibited circadian phase-dependent fatigue susceptibility on the rotarod, particularly at ZT0. Both exercised Clock\u039419 groups (ZT0 and ZT12) showed significant weight reduction compared to sedentary controls, indicating that endurance exercise may counteracts circadian disruption-induced weight gain independent of timing. In WT mice, evening exercise (ZT12) led to enhanced lipid regulation and better glucose tolerance. These time-dependent benefits were absent in Clock\u039419 mutants, demonstrating that the full metabolic advantages of exercise require a functional circadian clock. Notably, endurance training also partially restored serum HDL-C levels in Clock\u039419 mice, suggesting compensatory metabolic responses. Conclusions: Aligning endurance exercise with the body\u2019s internal clock provides greater metabolic benefits than untimed exercise. The circadian clock is essential for time-dependent improvements in glucose and lipid metabolism, although some beneficial effects occur independently of a functional clock.<\/jats:p>","DOI":"10.3390\/jfmk11020226","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:07:52Z","timestamp":1780326472000},"page":"226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-Dependent Endurance Exercise Improves Metabolic Health Through Circadian Rhythm Regulation in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Yanqing","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, NO. 130, Dongan Road, Xuhui District, Shanghai 200030, China"},{"name":"Institute of Bone and Joint Diseases, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, NO. 130, Dongan Road, Xuhui District, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoqing","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Bone and Joint Diseases, Fudan University, Shanghai 200032, China"},{"name":"Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9484-6415","authenticated-orcid":false,"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, NO. 130, Dongan Road, Xuhui District, Shanghai 200030, China"},{"name":"Institute of Bone and Joint Diseases, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxuan","family":"Hua","sequence":"additional","affiliation":[{"name":"Institute of Bone and Joint Diseases, Fudan University, Shanghai 200032, China"},{"name":"Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.aah4965","article-title":"Circadian time signatures of fitness and disease","volume":"354","author":"Bass","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41574-019-0210-x","article-title":"The circadian regulation of food intake","volume":"15","author":"Challet","year":"2019","journal-title":"Nat. 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