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饮食诱导肥胖中昼夜节律的失调。

Misalignment of Circadian Rhythms in Diet-Induced Obesity.

机构信息

Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.

Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.

出版信息

Adv Exp Med Biol. 2024;1460:27-71. doi: 10.1007/978-3-031-63657-8_2.

DOI:10.1007/978-3-031-63657-8_2
PMID:39287848
Abstract

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronize them with daily cycles. While the central clock in the suprachiasmatic nucleus (SCN) is mainly synchronized by the light/dark cycles, the peripheral clocks react to other stimuli, including the feeding/fasting state, nutrients, sleep-wake cycles, and physical activity. During the disruption of circadian rhythms due to genetic mutations or social and occupational obligations, incorrect arrangement between the internal clock system and environmental rhythms leads to the development of obesity. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition leads to uncoupling of the peripheral clocks from the central pacemaker and to the development of metabolic disorders. The strong coupling of the SCN to the light-dark cycle creates a situation of misalignment when food is ingested during the "wrong" time of day. Food-anticipatory activity is mediated by a self-sustained circadian timing, and its principal component is a food-entrainable oscillator. Modifying the time of feeding alone greatly affects body weight, whereas ketogenic diet (KD) influences circadian biology, through the modulation of clock gene expression. Night-eating behavior is one of the causes of circadian disruption, and night eaters have compulsive and uncontrolled eating with severe obesity. By contrast, time-restricted eating (TRE) restores circadian rhythms through maintaining an appropriate daily rhythm of the eating-fasting cycle. The hypothalamus has a crucial role in the regulation of energy balance rather than food intake. While circadian locomotor output cycles kaput (CLOCK) expression levels increase with high-fat diet-induced obesity, peroxisome proliferator-activated receptor-alpha (PPARα) increases the transcriptional level of brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1 (BMAL1) in obese subjects. In this context, effective timing of chronotherapies aiming to correct SCN-driven rhythms depends on an accurate assessment of the SCN phase. In fact, in a multi-oscillator system, local rhythmicity and its disruption reflects the disruption of either local clocks or central clocks, thus imposing rhythmicity on those local tissues, whereas misalignment of peripheral oscillators is due to exosome-based intercellular communication.Consequently, disruption of clock genes results in dyslipidemia, insulin resistance, and obesity, while light exposure during the daytime, food intake during the daytime, and sleeping during the biological night promote circadian alignment between the central and peripheral clocks. Thus, shift work is associated with an increased risk of obesity, diabetes, and cardiovascular diseases because of unusual eating times as well as unusual light exposure and disruption of the circadian rhythm.

摘要

生物钟的昼夜节律系统协调细胞和生理过程,并使它们与日常周期同步。虽然视交叉上核(SCN)中的中央时钟主要通过光/暗周期同步,但外周时钟对其他刺激(包括进食/禁食状态、营养、睡眠-觉醒周期和体力活动)作出反应。由于基因突变或社会和职业义务导致昼夜节律紊乱时,内部时钟系统与环境节律之间的安排不当会导致肥胖的发生。通过改变食物摄入时间和饮食成分导致中央时钟和外周时钟不同步,从而使外周时钟与中央起搏器解耦,并导致代谢紊乱。SCN 与光-暗周期的紧密耦合会导致在一天中的“错误”时间进食时出现错位。食物预期活动是由自我维持的昼夜节律机制介导的,其主要成分是食物可诱导的振荡器。仅改变进食时间就会极大地影响体重,而生酮饮食(KD)通过调节时钟基因表达来影响昼夜节律生物学。夜间进食行为是昼夜节律紊乱的原因之一,夜间进食者有强迫性和无法控制的进食行为,导致严重肥胖。相比之下,限时进食(TRE)通过保持适当的每日进食-禁食周期节律来恢复昼夜节律。下丘脑在调节能量平衡方面起着至关重要的作用,而不是调节食物摄入。虽然高脂肪饮食诱导肥胖时,时钟基因输出周期崩塌(CLOCK)的表达水平增加,但过氧化物酶体增殖物激活受体-α(PPARα)会增加肥胖患者大脑和肌肉芳香烃受体核转位蛋白(ARNT)样 1(BMAL1)的转录水平。在这种情况下,旨在纠正 SCN 驱动节律的时间疗法的有效时间取决于对 SCN 相位的准确评估。事实上,在多振荡器系统中,局部节律性及其破坏反映了局部时钟或中央时钟的破坏,从而对那些局部组织施加节律性,而外周振荡器的失准是由于基于外泌体的细胞间通讯。因此,时钟基因的破坏会导致血脂异常、胰岛素抵抗和肥胖,而白天光照、白天进食和生物夜间睡眠会促进中央时钟和外周时钟之间的昼夜节律同步。因此,轮班工作与肥胖、糖尿病和心血管疾病的风险增加有关,原因是进食时间不规律、光照不规律以及昼夜节律紊乱。

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