中国全科医学 ›› 2025, Vol. 28 ›› Issue (27): 3432-3440.DOI: 10.12114/j.issn.1007-9572.2024.0684

• 论著·健康管理·饮食与运动 • 上一篇    

频繁饮食对人体糖脂代谢及生物节律表达的影响研究

杨俊1, 麦布拜穆·艾斯卡尔1, 杨倩倩1, 李凯1, 尹高军2,*(), 蔡慧珍1,*()   

  1. 1.750004 宁夏回族自治区银川市,宁夏医科大学公共卫生学院
    2.750004 宁夏回族自治区银川市,宁夏医科大学总医院健康管理中心
  • 收稿日期:2025-02-18 修回日期:2025-04-23 出版日期:2025-09-20 发布日期:2025-07-22
  • 通讯作者: 尹高军, 蔡慧珍

  • 作者贡献:

    杨俊负责主要试验及数据分析、统计作图及论文的书写改正;麦布拜穆·艾斯卡尔负责部分试验;杨倩倩负责数据的收集和整理;李凯负责调查报告的实施,调查对象的选取;尹高军进行论文的修订及文章的质量控制与审查;蔡慧珍负责研究的构思与设计,对文章整体负责,监督管理。

  • 基金资助:
    国家自然科学基金资助项目(81973046,82360645)

Effects of Frequent Diets on Glucolipid Metabolism and Biorhythmic Expression in Humans

YANG Jun1, MAIBUBAIMU· Aisikaer1, YANG Qianqian1, LI Kai1, YIN Gaojun2,*(), CAI Huizhen1,*()   

  1. 1. School of Public Health, Ningxia Medical University, Yinchuan 750004, China
    2. Health Management Center, General Hospital of Ningxia Medical University, Yinchuan 750004, China
  • Received:2025-02-18 Revised:2025-04-23 Published:2025-09-20 Online:2025-07-22
  • Contact: YIN Gaojun, CAI Huizhen

摘要: 背景 糖脂代谢相关疾病发病率逐年上升,饮食模式被普遍认为与其发生密切相关。饮食不当会导致生物节律紊乱,这一过程又受到多种基因的调节。明确不同饮食方式的作用,对预防代谢疾病的发生至关重要。但是目前相关流行病学资料和人群研究的证据较少。 目的 探讨频繁饮食对人体糖脂代谢及生物节律表达的影响,为健康人群饮食频率与疾病风险研究提供思路。 方法 于2022年4—5月招募作息规律、饮食规律、零食摄入适中的18~29岁健康志愿者作为研究对象。将筛选出的20名健康志愿者简单随机分为三餐组(10名)和六餐组(10名)进行交叉干预。三餐组摄入3顿主食,进食时间分别为7:00、12:00、18:00;六餐组在三餐进食时间点之外,分别在10:00、15:00、20:00给予口服溶有75 g无水葡萄糖粉的300 mL糖水。两组单次干预时间为1 d,分别于8个时间点(7:00、8:00、10:00、12:00、13:00、16:00、20:00、次日2:00)采血样,检测血清中糖脂代谢相关指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、血糖、胰岛素、瘦素]及各节律基因(Clock、Bmal 1、Per 2、Cry 1、Ppar α和Sirt 1)的mRNA表达水平并比较。 结果 组别和时间对TG水平存在交互作用(F交互=2.277,P交互=0.032),组别在LDL-C水平上主效应显著(F组间=4.803,P组间=0.030),时间在TC水平上主效应显著(F时间=2.092,P时间=0.048);两组各时间点TC、TG、LDL-C、HDL-C水平比较,差异无统计学意义(P>0.05)。组别和时间对血糖水平存在交互作用(F交互=3.926,P交互=0.001),组别在胰岛素水平上主效应显著(F组间=12.240,P组间<0.001),时间在血糖、胰岛素、瘦素水平上主效应均显著(F时间=10.840、2.399、4.347,P时间<0.05);六餐组12:00、20:00血糖水平及10:00、16:00胰岛素水平高于三餐组,16:00瘦素水平低于三餐组(P<0.05)。组别和时间对Cry 1基因的mRNA表达水平存在交互作用(F交互=30.250,P交互<0.001),组别在Clock、Bmal 1、Per 2、Cry 1、Ppar α、Sirt 1基因的mRNA表达水平上主效应均显著(P组间<0.05),时间在Bmal 1、Per 2、Cry 1、Sirt 1基因的mRNA表达水平上主效应均显著(P时间<0.05);六餐组8:00、13:00时Clock基因的mRNA表达水平,8:00、16:00和次日2:00时Per 2基因的mRNA表达水平,7:00、8:00、10:00时Cry 1基因的mRNA表达水平高于三餐组(P<0.05);六餐组10:00、12:00和13:00时Bmal 1基因的mRNA表达水平,20:00和次日2:00时Cry 1基因的mRNA表达水平低于三餐组(P<0.05);两组各时间点Ppar α基因、Sirt 1基因的mRNA表达水平比较,差异无统计学意义(P>0.05)。 结论 频繁进食的六餐组会引起胰岛素和血糖水平升高,调节机制失衡,造成人体机体糖代谢水平稳态失衡。同时会影响各时钟基因水平的表达、相位和振幅,导致机体节律紊乱。

关键词: 代谢, 糖脂代谢, 生物节律, 饮食频率, 节律基因, 交叉干预, 多元方差分析

Abstract:

Background

Prevalence of glycolipid metabolism disorders is rising annually. Dietary patterns are recognized as key modulators of their pathogenesis. Improper eating habits cause circadian disruption, which can be mediated by multiple genes. Clarifying the role of different dietary methods is crucial to preventing the occurrence of metabolic diseases. However, relevant epidemiological data and data of population studies are scant.

Objective

To investigate the effects of dietary frequency on human glycolipid metabolism and circadian gene expressions, thereby providing insights into the relationship between dietary frequency and disease risk in healthy populations.

Methods

Healthy volunteers aged 18-29 years with regular sleep-wake cycles, regular dietary, and moderate snack intake were recruited between April and May 2022. Twenty eligible participants were randomized into two groups: a three-meal group (n=10) and a six-meal group (n=10) for a crossover intervention. Participants in the three-meal group consumed main meals at 7: 00, 12: 00, and 18: 00. Those in the six-meal group received three additional glucose challenges (75 g anhydrous glucose dissolved in 300 mL of water) at 10: 00, 15: 00, and 20: 00. Each intervention lasted 24 hours. Blood samples were collected at eight timepoints (7: 00, 8: 00, 10: 00, 12: 00, 13: 00, 16: 00, 20: 00, 2: 00) to analyze serum metabolic markers, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, insulin, and leptin. The mRNA expression levels of circadian genes were detected (Clock, Bmal 1, Per 2, Cry 1, Ppar α, Sirt 1) .

Results

A significant interaction effect between group and time was observed on TG levels (Finteraction =2.277, Pinteraction =0.032). A significant main effect of group presented on LDL-C levels (Fgroup=4.803, Pgroup=0.030), while time exhibited a significant main effect on TC levels (Ftime=2.092, Ptime=0.048). No significant differences in TC, TG, LDL-C, or HDL-C levels were observed between the two groups at any time points (P>0.05). A significant interaction effect between group and time was identified for blood glucose levels (Finteraction =3.926, Pinteraction =0.001). The group showed a significant main effect on insulin levels (Fgroup=12.240, Pgroup<0.001), and time demonstrated significant main effects on blood glucose, insulin, and leptin levels (Ftime=10.840, 2.399, and 4.347, respectively; Ptime<0.05). Participants in the six-meal group exhibited higher blood glucose levels at 12: 00 and 20: 00, elevated insulin levels at 10: 00 and 16: 00, and lower leptin levels at 16: 00 compared to the three-meal group (P<0.05). A significant interaction effect between group and time was observed for the mRNA expression of Cry 1 (Finteraction =30.250, Pinteraction<0.001). Significant main effects of group were detected for the mRNA expressions of Clock, Bmal 1, Per 2, Cry 1, Ppar α, and Sirt 1 (Pgroup<0.05), while significant main effects of time were noted for the mRNA expressions of Bmal 1, Per 2, Cry 1, and Sirt 1 (Ptime<0.05). Participants in the six-meal group displayed significantly higher mRNA expressions of Clock at 8: 00 and 13: 00, Per 2 at 8: 00, 16: 00, and 2: 00, and Cry 1 at 7: 00, 8: 00, and 10: 00 compared to the three-meal group (P<0.05). Conversely, significantly lower expressions of Bmal 1 at 10: 00, 12: 00, and 13: 00, and Cry 1 at 20: 00 and 2: 00 were observed in the six-meal group (P<0.05). No significant differences in the mRNA expressions of Ppar α and Sirt 1 were detected between groups at any time points (P>0.05) .

Conclusion

Frequent six-meal consumption elevates insulin and glucose levels, disrupts metabolic homeostasis, and alters circadian clock gene expression in phase and amplitude. These changes induce glucose metabolism dysregulation, leading to circadian rhythm disruption.

Key words: Metabolism, Glycolipid metabolism, Biorhythm, Dietary frequency, Circadian clock genes, Crossover intervention, Multivariate analysis of variance

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