{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:20Z","timestamp":1760060120733,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BioClock Consortium","award":["1292.19.077","ZonMW 459001021"],"award-info":[{"award-number":["1292.19.077","ZonMW 459001021"]}]},{"name":"Netherlands-Canada Type 2 Diabetes Research Consortium","award":["1292.19.077","ZonMW 459001021"],"award-info":[{"award-number":["1292.19.077","ZonMW 459001021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Excess caloric intake and insufficient physical activity are the two major drivers underlying the global obesity and type 2 diabetes mellitus epidemics. However, circadian misalignment of caloric intake and physical activity, as commonly experienced by nightshift workers, can also have detrimental effects on body weight and glucose homeostasis. We have previously reported that combined restriction of eating and voluntary wheel running to the inactive phase (i.e., a rat model for circadian misalignment) shifted liver and muscle clock rhythms by ~12 h and prevented the reduction in the amplitude of the muscle clock oscillation otherwise induced by light-phase feeding. Here, we extended on these findings and investigated how a high-fat diet (HFD) affects body composition and liver and muscle clock gene rhythms in male Wistar rats while restricting both eating and exercise to either the inactive or active phase. To do this, we used four experimental conditions: sedentary controls with no wheel access on a non-obesogenic diet (NR), sedentary controls with no wheel access on an HFD (NR-H), and two experimental groups on an HFD with simultaneous access to a running wheel and HFD time-restricted to either the light phase (light-run-light-fed + HFD, LRLF-H) or the dark phase (dark-run-dark-fed + HFD. DRDF-H). Consumption of an HFD did not alter the daily running distance of the time-restricted groups but did increase the running intensity in the LRLF-H group compared to a previously published LRLF chow fed group. However, no such increase was observed for the DRDF-H group. LRLF-H ameliorated light phase-induced disturbances in the soleus clock more effectively than under chow conditions and had a protective effect against HFD-induced changes in liver clock gene expression. Together with (our) previously published results, these data suggest that eating healthy and being active at the wrong time of the day can be as detrimental as eating unhealthy and being active at the right time of the day.<\/jats:p>","DOI":"10.3390\/ijms26157658","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T09:56:42Z","timestamp":1754647002000},"page":"7658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining Time-Restricted Wheel Running and Feeding During the Light Phase Increases Running Intensity Under High-Fat Diet Conditions Without Altering the Total Amount of Daily Running"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3404-9159","authenticated-orcid":false,"given":"Ayano","family":"Shiba","sequence":"first","affiliation":[{"name":"Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"},{"name":"Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Tandari","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"},{"name":"Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewout","family":"Foppen","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"},{"name":"Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-4615","authenticated-orcid":false,"given":"Chun-Xia","family":"Yi","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"},{"name":"Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0453-2568","authenticated-orcid":false,"given":"Joram D.","family":"Mul","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute for Life Sciences, Faculty of Science, Science Park 904, 1098 XH Amsterdam, The Netherlands"},{"name":"Centre for Urban Mental Health, University of Amsterdam, 1098 XH Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-5140","authenticated-orcid":false,"given":"Dirk Jan","family":"Stenvers","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-8453","authenticated-orcid":false,"given":"Andries","family":"Kalsbeek","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"},{"name":"Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1210\/jc.2015-3924","article-title":"Effects of the Internal Circadian System and Circadian Misalignment on Glucose Tolerance in Chronic Shift Workers","volume":"101","author":"Morris","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"de Goede, P., Foppen, E., Ritsema, W.I.G.R., Korpel, N.L., Yi, C.-X., and Kalsbeek, A. (2019). Time-Restricted Feeding Improves Glucose Tolerance in Rats, but Only When in Line with the Circadian Timing System. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00554"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/ijo.2016.80","article-title":"The acute effects of time-of-day-dependent high fat feeding on whole body metabolic flexibility in mice","volume":"40","author":"Joo","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.cell.2017.01.025","article-title":"Gut-Brain Cross-Talk in Metabolic Control","volume":"168","author":"Clemmensen","year":"2017","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1113\/jphysiol.2008.159566","article-title":"High-fat feeding alters the clock synchronization to light","volume":"586","author":"Mendoza","year":"2008","journal-title":"J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1002\/oby.22832","article-title":"Synergistic Effect of Feeding Time and Diet on Hepatic Steatosis and Gene Expression in Male Wistar Rats","volume":"28","author":"Oosterman","year":"2020","journal-title":"Obesity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.nbscr.2017.09.002","article-title":"Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks","volume":"4","author":"Sen","year":"2018","journal-title":"Neurobiol. Sleep Circadian Rhythm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1152\/japplphysiol.00737.2018","article-title":"Voluntary wheel running in the late dark phase ameliorates diet-induced obesity in mice without altering insulin action","volume":"126","author":"Dalbram","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2218510120","DOI":"10.1073\/pnas.2218510120","article-title":"Time of day determines postexercise metabolism in mouse adipose tissue","volume":"120","author":"Pendergrast","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cmet.2019.03.013","article-title":"Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis","volume":"30","author":"Sato","year":"2019","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sch\u00f6nke, M., Ying, Z., Kovynev, A., In Het Panhuis, W., Binnendijk, A., van der Poel, S., Pronk, A.C.M., Streefland, T.C.M., Hoekstra, M., and Kooijman, S. (2023). Time to run: Late rather than early exercise training in mice remodels the gut microbiome and reduces atherosclerosis development. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 37.","DOI":"10.1096\/fj.202201304R"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pendergast, J.S., Branecky, K.L., Huang, R., Niswender, K.D., and Yamazaki, S. (2014). Wheel-running activity modulates circadian organization and the daily rhythm of eating behavior. Front. Psychol., 5.","DOI":"10.3389\/fpsyg.2014.00177"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Shiba, A., de Goede, P., Tandari, R., Foppen, E., Korpel, N.L., Coopmans, T.V., Hellings, T.P., Jansen, M.W., Ruitenberg, A., and Ritsema, W.I.G.R. (2024). Synergy between time-restricted feeding and time-restricted running is necessary to shift the muscle clock in male wistar rats. Neurobiol. Sleep Circadian Rhythm., 17.","DOI":"10.1016\/j.nbscr.2024.100106"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/s42255-023-00826-7","article-title":"Daytime-restricted feeding enhances running endurance without prior exercise in mice","volume":"5","author":"Xin","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1007\/s00125-021-05477-5","article-title":"The effect of morning vs evening exercise training on glycaemic control and serum metabolites in overweight\/obese men: A randomised trial","volume":"64","author":"Moholdt","year":"2021","journal-title":"Diabetologia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E513","DOI":"10.1152\/ajpendo.00129.2023","article-title":"Time-restricted feeding combined with resistance exercise prevents obesity and improves lipid metabolism in the liver of mice fed a high-fat diet","volume":"325","author":"Chaix","year":"2023","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1113\/JP280820","article-title":"Time-restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high-fat diet","volume":"600","author":"Vieira","year":"2022","journal-title":"J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.18632\/aging.101857","article-title":"Running wheel access fails to resolve impaired sustainable health in mice feeding a high fat sucrose diet","volume":"11","author":"Reijne","year":"2019","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Deng, G., Jiang, Z., Lu, H., Lu, N., Zhu, R., Zhu, C., Zhou, P., and Tang, X. (2023). A Study on the Amelioration of Circadian Rhythm Disorders in Fat Mice Using High-Protein Diets. Nutrients, 15.","DOI":"10.3390\/nu15153459"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.cmet.2010.10.005","article-title":"PER2 Controls Lipid Metabolism by Direct Regulation of PPAR\u03b3","volume":"12","author":"Grimaldi","year":"2010","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5088","DOI":"10.1523\/JNEUROSCI.0052-18.2018","article-title":"Time-Restricted Feeding Prevents Ablation of Diurnal Rhythms in Gastric Vagal Afferent Mechanosensitivity Observed in High-Fat Diet-Induced Obese Mice","volume":"38","author":"Kentish","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Begemann, K., and Oster, H. (2022). Snack timing affects tissue clock and metabolic responses in male mice. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.956641"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, R., Zhang, Z., Ma, J., Liu, B., Huang, Z., Hu, G., Huang, J., Xu, Y., and Wang, G.-Z. (2024). Circadian-driven tissue specificity is constrained under caloric restricted feeding conditions. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06421-0"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100984","DOI":"10.1016\/j.mam.2021.100984","article-title":"Circadian rhythms in the tissue-specificity from metabolism to immunity: Insights from omics studies","volume":"80","author":"Kinouchi","year":"2021","journal-title":"Mol. Aspects Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.cmet.2022.12.006","article-title":"Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals","volume":"35","author":"Deota","year":"2023","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/9780470942390.mo100160","article-title":"Exercise Performance Tests in Mice","volume":"1","author":"Marcaletti","year":"2011","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1152\/jappl.2001.90.5.1900","article-title":"Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse","volume":"90","author":"Allen","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.physbeh.2016.04.033","article-title":"Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running","volume":"161","author":"Claghorn","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Manzanares, G., Brito-da-Silva, G., and Gandra, P.G. (2018). Voluntary wheel running: Patterns and physiological effects in mice. Braz. J. Med. Biol. Res., 52.","DOI":"10.1590\/1414-431x20187830"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1242\/jeb.028886","article-title":"Endurance capacity of mice selectively bred for high voluntary wheel running","volume":"212","author":"Meek","year":"2009","journal-title":"J. Exp. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1152\/jappl.1979.47.6.1278","article-title":"Maximum oxygen consumption of rats and its changes with various experimental procedures","volume":"47","author":"Bedford","year":"1979","journal-title":"J. Appl. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1111\/ejn.13193","article-title":"Neurochemical and behavioral indices of exercise reward are independent of exercise controllability","volume":"43","author":"Herrera","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s00774-007-0831-3","article-title":"Endurance treadmill running training benefits the biomaterial quality of bone in growing male Wistar rats","volume":"26","author":"Huang","year":"2008","journal-title":"J. Bone Miner. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF00587471","article-title":"Effects of training on VO2 max and VO2 during two running intensities in rats","volume":"386","author":"Patch","year":"1980","journal-title":"Pflugers Arch."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jshs.2019.09.008","article-title":"Impacts of exercise intervention on various diseases in rats","volume":"9","author":"Wang","year":"2020","journal-title":"J. Sport Health Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4594956","DOI":"10.1155\/2022\/4594956","article-title":"Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.metabol.2014.05.010","article-title":"Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change","volume":"63","author":"Hulmi","year":"2014","journal-title":"Metabolism"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/hep.27409","article-title":"Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis","volume":"61","author":"Wang","year":"2015","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112004","DOI":"10.1016\/j.mad.2024.112004","article-title":"Differential Plin5 response to high-fat diet in cardiomyocytes isolated from young and aged mice","volume":"222","author":"Baumgarten","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1194\/jlr.M038992","article-title":"Fatty acids regulate perilipin5 in muscle by activating PPAR\u03b4","volume":"54","author":"Berg","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s12013-018-0860-7","article-title":"The Effects of Resveratrol, Metformin, Cold and Strength Training on the Level of Perilipin 5 in the Heart, Skeletal Muscle and Brown Adipose Tissues in Mouse","volume":"76","author":"Mehdi","year":"2018","journal-title":"Cell Biochem. Biophys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.2337\/db14-1035","article-title":"Perilipin 5\u2013Driven Lipid Droplet Accumulation in Skeletal Muscle Stimulates the Expression of Fibroblast Growth Factor 21","volume":"64","author":"Harris","year":"2015","journal-title":"Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"155137","DOI":"10.1016\/j.metabol.2022.155137","article-title":"Effects of aerobic exercise on fibroblast growth factor 21 in overweight and obesity. A systematic review","volume":"129","author":"Tam","year":"2022","journal-title":"Metabolism"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"van Eenige, R., Verhave, P.S., Koemans, P.J., Tiebosch, I.A.C.W., Rensen, P.C.N., and Kooijman, S. (2020). RandoMice, a novel, user-friendly randomization tool in animal research. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237096"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mo\u0161kon, M. (2020). CosinorPy: A python package for cosinor-based rhythmometry. BMC Bioinform., 21.","DOI":"10.1186\/s12859-020-03830-w"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:58Z","timestamp":1760034358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":45,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157658"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157658","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,8,7]]}}}