Shiba Ayano, Tandari Roberta, Foppen Ewout, Yi Chun-Xia, Mul Joram D, Stenvers Dirk Jan, Kalsbeek Andries
Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Int J Mol Sci. 2025 Aug 7;26(15):7658. doi: 10.3390/ijms26157658.
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.
热量摄入过多和身体活动不足是全球肥胖症和2型糖尿病流行的两大主要驱动因素。然而，夜班工作者常见的热量摄入和身体活动的昼夜节律失调，也会对体重和葡萄糖稳态产生不利影响。我们之前报道过，将进食和自愿轮转跑步限制在不活跃期（即昼夜节律失调的大鼠模型）会使肝脏和肌肉的生物钟节律 shift 约12小时，并防止光期进食否则会引起的肌肉生物钟振荡幅度减小。在此，我们扩展了这些发现，并研究了高脂饮食（HFD）如何影响雄性Wistar大鼠的身体成分以及肝脏和肌肉生物钟基因节律，同时将进食和运动限制在不活跃期或活跃期。为此，我们使用了四种实验条件：非致肥胖饮食且无轮转跑步机会的久坐对照组（NR）、高脂饮食且无轮转跑步机会的久坐对照组（NR-H），以及两个高脂饮食实验组，同时可使用轮转跑步装置且高脂饮食时间限制在光期（光期跑步-光期喂食 + HFD，LRLF-H）或暗期（暗期跑步-暗期喂食 + HFD，DRDF-H）。食用高脂饮食并未改变时间限制组的每日跑步距离，但与之前发表的LRLF普通饲料喂养组相比，LRLF-H组的跑步强度确实增加了。然而，DRDF-H组未观察到这种增加。与普通饲料条件相比，LRLF-H更有效地改善了比目鱼肌生物钟在光期诱导的紊乱，并对高脂饮食引起的肝脏生物钟基因表达变化具有保护作用。连同我们之前发表的结果，这些数据表明，在一天中错误的时间吃不健康的食物并进行运动，可能与在一天中正确的时间吃不健康的食物并进行运动一样有害。
