Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China.
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China.
J Nutr Biochem. 2022 Dec;110:109128. doi: 10.1016/j.jnutbio.2022.109128. Epub 2022 Aug 15.
Circadian rhythms, type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are closely related and interacted with each other. We have previously showed circadian disruption aggravated progression of AD in T2DM mice. Time-restricted feeding (TRF) is shown to be a potential synchronizer. This study aims to determine whether TRF has a protective effect against the circadian disruption-aggravated progression of AD in T2DM. 6-week-old male diabetic (db/db) mice and wildtype (wt/wt) mice were kept under normal 12:12 light/dark cycles or altered 6:18 light/dark cycles (dark extended to 18 h) with or without TRF (food restricted to 8 h during the active (dark) period). After 8 weeks, three behavioral tests (open field test, novel object recognition test, barnes maze test) were performed and the circadian gene expression, body weight, lipid levels and AD-associated tau phosphorylation were evaluated. We found altered light/dark cycles contributed to disruptive circadian rhythms in the hippocampus of db/db mice, while TRF prevented this effect. TRF also ameliorated circadian disruption-aggravated increased body weight and lipid accumulation in db/db mice. Importantly, the db/db mice under circadian disruption showed impaired cognition accompanied by increased tau phosphorylation, whereas TRF reversed these changes. The altered light/dark cycles only affected circadian rhythms but not other indicators like plasma/liver lipids, cognition and tau phosphorylation in the wt/wt mice. Collectively, TRF has a protective effect against altered light/dark cycles-aggravated AD progression in diabetic mice.
昼夜节律、2 型糖尿病（T2DM）和阿尔茨海默病（AD）密切相关并相互作用。我们之前的研究表明，昼夜节律紊乱会加重 T2DM 小鼠 AD 的进展。限时喂养（TRF）被证明是一种潜在的同步器。本研究旨在确定 TRF 是否对 T2DM 中昼夜节律紊乱加重 AD 进展具有保护作用。将 6 周龄雄性糖尿病（db/db）小鼠和野生型（wt/wt）小鼠分别置于正常的 12:12 光照/黑暗周期或改变的 6:18 光照/黑暗周期（黑暗延长至 18 小时），并进行或不进行 TRF（在活动（黑暗）期内将食物限制在 8 小时内）。8 周后，进行了三项行为测试（旷场测试、新物体识别测试、巴恩斯迷宫测试），并评估了昼夜节律基因表达、体重、血脂水平和 AD 相关的 tau 磷酸化。我们发现改变的光照/黑暗周期导致 db/db 小鼠海马体的昼夜节律紊乱，而 TRF 可防止这种影响。TRF 还改善了 db/db 小鼠中昼夜节律紊乱加剧的体重增加和脂质积累。重要的是，昼夜节律紊乱的 db/db 小鼠表现出认知障碍，伴有 tau 磷酸化增加，而 TRF 则逆转了这些变化。改变的光照/黑暗周期仅影响昼夜节律，而不影响 wt/wt 小鼠的其他指标，如血浆/肝脏脂质、认知和 tau 磷酸化。总之，TRF 对糖尿病小鼠改变的光照/黑暗周期加重 AD 进展具有保护作用。
