ABSTRACT

Obesity is a global health threat and a risk factor for several metabolic conditions. Though circadian dysfunction has been considered among the multiple causes of obesity, little work has been done to explore the relationship between obesity, circadian dysfunction, and sexual dimorphism. The Neotomodon alstoni mouse is a suitable model for such research. This study employed N. alstoni mice in a chronobiological analysis to determine whether there is circadian desynchronization of relative PER1 and BMAL1 protein levels in the hypothalamus, liver, visceral white adipose tissue, kidney, and heart. It also compared differences between sexes and lean and obese N. alstoni adult mice, by recording behavior and daily circulating serum melatonin as markers of circadian output. We found that obese mice display reduced locomotor activity. Additionally, Cosinor analyses of the relative expression of PER1 and BMAL1 show differences between lean and obese mice in a sex-linked manner. The PER1 24 h rhythm was absent in all tissues of obese males and significant in the tissues of obese females. The BMAL1 24 h rhythm also was significant in most of the tissues tested in lean males, whereas it was significant and shifted the acrophase (peak time of rhythm) in most of the tissues in obese females. Both lean male and female mice showed a rhythmic 24 h pattern of circulating serum melatonin. This daily profile was not only absent in obese mice of both sexes but showed sexual dimorphism. Obese male mice showed lower circulating levels of melatonin compared to lean male mice, but they were higher in obese females compared to lean females. Our results suggest that obesity in N. alstoni is associated with an internal circadian desynchronization in a sex-dependent manner. Overall, this study reinforces the need for further research on the neuroendocrinology of obesity and circadian rhythms using this biological model.

 抽象的

肥胖是全球健康威胁，也是多种代谢疾病的危险因素。尽管昼夜节律功能障碍被认为是肥胖的多种原因之一，但很少有人研究肥胖、昼夜节律功能障碍和性别二态性之间的关系。 Neotomodon alstoni小鼠是此类研究的合适模型。本研究采用N. alstoni小鼠进行时间生物学分析，以确定下丘脑、肝脏、内脏白色脂肪组织、肾脏和心脏中相对 PER1 和 BMAL1 蛋白水平是否存在昼夜不同步。它还通过记录行为和每日循环血清褪黑激素作为昼夜节律输出的标记，比较了性别以及瘦和肥胖的阿尔斯托尼成年小鼠之间的差异。我们发现肥胖小鼠的运动活动减少。此外，PER1 和 BMAL1 相对表达的 Cosinor 分析显示瘦小鼠和肥胖小鼠之间存在性别相关的差异。肥胖男性的所有组织中均不存在 PER1 24 小时节律，而在肥胖女性的组织中则显着。 BMAL1 24 小时节律在瘦男性测试的大多数组织中也很显着，而在肥胖女性的大多数组织中，BMAL1 24 小时节律很显着并且改变了顶峰期（节律的峰值时间）。瘦雄性和雌性小鼠均表现出 24 小时有节奏的血清褪黑激素循环模式。这种每日特征不仅在两性肥胖小鼠中不存在，而且表现出性别二态性。与瘦雄性小鼠相比，肥胖雄性小鼠的褪黑激素循环水平较低，但与瘦雌性小鼠相比，肥胖雌性小鼠的褪黑激素循环水平较高。我们的结果表明， N中的肥胖。 阿尔斯托尼与性别依赖性的内部昼夜节律失同步有关。总的来说，这项研究强调了利用这种生物模型对肥胖和昼夜节律的神经内分泌学进行进一步研究的必要性。