Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia, USA.
Department of Medicine, Division of Oncology/Hematology, West Virginia, USA.
Chronobiol Int. 2022 Apr;39(4):535-546. doi: 10.1080/07420528.2021.2011306. Epub 2021 Dec 12.
Disruption of circadian rhythms has detrimental host consequences. Indeed, both clinical and foundational science demonstrate a clear relationship between disruption of circadian rhythms and cancer initiation and progression. Because timing of food intake can act as a zeitgeber (i.e., entrainment signal) for the circadian clock, and most individuals in the developed world have access to food at all times of the day in a "24/7" society, we sought to determine the effects of timing of food intake on mammary tumor growth. We hypothesized that restricting access to food to during the inactive phase would accelerate tumor growth. Adult female Balb/C mice received a unilateral orthotopic injection of murine mammary carcinoma 4T1 cells into the ninth inguinal mammary gland. Beginning on the day of tumor injection and continuing until the end of the experiment, mice were food restricted to their active phase (ZT12 (lights off)- ZT0 (lights on), inactive phase (ZT0 - ZT12), or had access to food. Mice that were food restricted to their inactive phase displayed a significant increase in body mass on days 7 and 14 of tumor growth relative to active phase or fed mice. Additionally, mice fed during their inactive phase demonstrated a 20% reduction in food consumption relative to mice fed during their active phase and a 17% reduction in food consumption relative to fed mice. Tumor volume was not significantly different between groups. However, food restricting mice to their inactive phase increased mammary tumor growth efficiency (i.e., mg of tumor mass per gram of food intake) relative to mice fed during the active phase and approached significance ( = .06) relative to fed mice. To determine a potential explanation for the increased tumor growth efficiency, we examined rhythms of activity and body temperature. Mice fed during the inactive phase displayed significantly disrupted daily activity and body temperature rhythms relative to both other feeding regimens. Together, these data demonstrate that improperly timed food intake can have detrimental consequences on mammary tumor growth likely via disrupted circadian rhythms.
昼夜节律紊乱对宿主有不利影响。事实上，临床和基础科学都表明，昼夜节律紊乱与癌症的发生和进展之间存在明显的关系。由于进食时间可以作为生物钟的授时信号（即同步信号），而且在“24/7”社会中，大多数发达国家的人都可以随时进食，因此，我们试图确定进食时间对乳腺肿瘤生长的影响。我们假设限制食物摄入只在非活动期进行会加速肿瘤生长。成年雌性 Balb/C 小鼠在第九腹股沟乳腺中接受单侧同源注射鼠乳腺肿瘤 4T1 细胞。从肿瘤注射的当天开始，并且持续到实验结束，将小鼠限制在其活动期（ZT12（熄灯）-ZT0（开灯），非活动期（ZT0-ZT12）或可以进食。与活动期或自由进食的小鼠相比，在非活动期限制进食的小鼠在肿瘤生长的第 7 天和第 14 天体重明显增加。此外，在非活动期进食的小鼠与在活动期进食的小鼠相比，食物摄入量减少了 20%，与自由进食的小鼠相比，食物摄入量减少了 17%。肿瘤体积在各组之间没有显著差异。然而，将小鼠限制在非活动期进食会增加乳腺肿瘤生长效率（即，每克食物摄入的肿瘤质量），与在活动期进食的小鼠相比接近显著（=0.06），与自由进食的小鼠相比。为了确定肿瘤生长效率增加的潜在原因，我们检查了活动和体温的节律。在非活动期进食的小鼠与其他两种喂养方案相比，其日常活动和体温节律明显受到干扰。这些数据共同表明，不适当的进食时间可能会通过打乱昼夜节律对乳腺肿瘤生长产生不利影响。
