Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, 76230, México.
Unidad Multidisciplinaria de Docencia e Investigación, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, 76230, México.
Sci Rep. 2020 Jun 22;10(1):10036. doi: 10.1038/s41598-020-66538-0.
Circadian rhythms are the product of the interaction of molecular clocks and environmental signals, such as light-dark cycles and eating-fasting cycles. Several studies have demonstrated that the circadian rhythm of peripheral clocks, and behavioural and metabolic mediators are re-synchronized in rodents fed under metabolic challenges, such as hyper- or hypocaloric diets and subjected to time-restricted feeding protocols. Despite the metabolic challenge, these approaches improve the metabolic status, raising the enquiry whether removing progressively the hypocaloric challenge in a time-restricted feeding protocol leads to metabolic benefits by the synchronizing effect. To address this issue, we compared the effects of two time-restricted feeding protocols, one involved hypocaloric intake during the entire protocol (HCT) and the other implied a progressive intake accomplishing a normocaloric intake at the end of the protocol (NCT) on several behavioural, metabolic, and molecular rhythmic parameters. We observed that the food anticipatory activity (FAA) was driven and maintained in both HCT and NCT. Resynchronization of hepatic molecular clock, free fatty acids (FFAs), and FGF21 was elicited closely by HCT and NCT. We further observed that the fasting cycles involved in both protocols promoted ketone body production, preferentially beta-hydroxybutyrate in HCT, whereas acetoacetate was favoured in NCT before access to food. These findings demonstrate that time-restricted feeding does not require a sustained calorie restriction for promoting and maintaining the synchronization of the metabolic and behavioural circadian clock, and suggest that metabolic modulators, such as FFAs and FGF21, could contribute to FAA expression.
昼夜节律是分子钟和环境信号（如光-暗周期和进食-禁食周期）相互作用的产物。几项研究表明，在代谢挑战下，如高卡路里或低卡路里饮食和限时进食方案，啮齿动物的外周时钟节律、行为和代谢介质会重新同步。尽管存在代谢挑战，但这些方法改善了代谢状态，这引发了一个疑问，即在限时进食方案中逐渐去除低卡路里挑战是否会通过同步作用带来代谢益处。为了解决这个问题，我们比较了两种限时进食方案的效果，一种方案在整个方案中涉及低卡路里摄入（HCT），另一种方案则意味着在方案结束时逐渐摄入以达到正常卡路里摄入（NCT），以评估它们对几种行为、代谢和分子节律参数的影响。我们观察到，两种方案都能驱动和维持食物 anticipatory activity (FAA)。HCT 和 NCT 都能紧密地重新同步肝脏分子钟、游离脂肪酸 (FFAs) 和 FGF21。我们还观察到，两种方案中的禁食周期都促进了酮体的产生，在 HCT 中主要是β-羟基丁酸，而在 NCT 中，在进食前优先产生乙酰乙酸盐。这些发现表明，限时进食并不需要持续的卡路里限制来促进和维持代谢和行为昼夜节律的同步，并且表明代谢调节剂，如 FFAs 和 FGF21，可能有助于 FAA 的表达。
