食品科学 ›› 2023, Vol. 44 ›› Issue (23): 95-103.doi: 10.7506/spkx1002-6630-20221122-261

• 营养卫生 • 上一篇    下一篇

高蛋白日粮对肥胖小鼠脂代谢昼夜节律的调节作用

江芷晴, 邓国良, 曾凡航, 邵茹, 诸荣翔, 唐雪   

  1. (江南大学食品学院,江苏 无锡 214122)
  • 出版日期:2023-12-15 发布日期:2024-01-02
  • 基金资助:
    国家自然科学基金青年科学基金项目(31901679)

Regulatory Effect of High-Protein Diet on Circadian Rhythm of Lipid Metabolism in Obese Mice

JIANG Zhiqing, DENG Guoliang, ZENG Fanhang, SHAO Ru, ZHU Rongxiang, TANG Xue   

  1. (School of Food Science and Technology, Jiangnan University, Wuxi 214122, China)
  • Online:2023-12-15 Published:2024-01-02

摘要: 目的:研究高蛋白日粮对高脂诱导的肥胖小鼠脂代谢昼夜节律紊乱的调节作用。方法:120 只SPF级C57BL/6J小鼠随机分成正常组、高脂组和高脂高蛋白组。干预第4周和第12周时监测小鼠活体代谢状态,饲养结束后分别于2 时、8 时、14 时和20 时处死小鼠,测定血脂和肝脂水平以及肝脏脂肪合成与分解代谢和生物钟相关基因的表达并分析昼夜节律变化规律。结果:高脂饲喂能够引起小鼠体质量和肥胖指数增加,活动期自主活动量和热量消耗减少。同时,伴随着血脂紊乱及肝脏脂质水平异常升高,具体表现为肝脏脂肪合成代谢关键酶乙酰辅酶A羧化酶和脂肪酸合成酶基因在活动期和休息期持续高水平表达,而脂肪分解代谢关键酶激素敏感性脂酶和乙酰辅酶A氧化酶基因表达量升高缓慢,昼夜差异规律改变。与高脂干预相比,高蛋白干预可明显增加活动期自主活动量和能量消耗,恢复脂肪合成酶基因活动期高、休息期低的表达节律,脂肪分解代谢关键酶基因ACOX亦在摄食后高水平表达,表现出明显的昼夜节律。进一步分析表明,高蛋白干预改善高脂所致的脂代谢节律紊乱与调节肝脏时钟基因即昼夜节律运动输出周期故障蛋白(circadian locomotor output cycle kaput,CLOCK)与脑和肌肉芳香烃受体核转运体样蛋白1(brain and muscle-Arnt-like protein 1,BMAL1)基因的表达密切相关。结论:高蛋白膳食可以缓解高脂饮食引起的肝脏生物钟紊乱,通过稳定昼夜节律改善小鼠肝脏脂代谢紊乱。

关键词: 高蛋白日粮;脂代谢;昼夜节律;肝脏

Abstract: This study aimed to investigate the regulatory effect of high-protein diet on circadian rhythm disturbances of lipid metabolism in obese mice induced by high-fat diet. Totally 120 specific pathogen-free (SPF)-grade C57BL/6J mice were randomly divided into normal, high-fat and high-fat/high-protein groups. The metabolic status of mice was monitored at the 4th and 12th week of intervention, and mice were sacrificed at 2, 8, 14, and 20 o’clock after completion of feeding. Lipid levels in blood and liver, the expression of genes related to fat anabolism and catabolism and the expression of circadian rhythm-related genes were measured, and circadian rhythm changes were analyzed. The results showed that high-fat feeding caused an increase in body mass and obesity index and a decrease in voluntary activity and caloric expenditure during the active period. The changes were accompanied by dyslipidemia and an abnormal increase in liver lipid levels, manifested by continuous gene expression of acetyl-CoA carboxylase and fatty acid synthetase, key enzymes involved in fat anabolism in liver, at high levels during the active and resting periods, a slow increase in the gene expression of sensitive lipase and acetyl-CoA oxidase, key enzymes involved in fat catabolism in liver, and changes in the diurnal variation pattern. Compared with high-fat intervention, high-protein intervention significantly increased the amount of voluntary activity and energy expenditure during the active period, restored the expression rhythm of fat synthase that was higher during the active period and lower during the rest period, and resulted in high-level expression of ACOX, a key enzyme gene involved in fat catabolism, after ingestion, showing obvious circadian rhythms. Further analysis showed that the improvement effects of high-protein intervention on circadian rhythm disorders of lipid metabolism caused by high-fat diet were closely related to the regulation of the expression of two clock genes in liver, circadian locomotor output cycle kaput (CLOCK) and brain and muscle-Arnt-like protein 1 (BMAL1). In conclusion, high-protein diets can alleviate biological clock disorders in liver induced by high-fat diets and ameliorate hepatic lipid metabolism disorders in mice by stabilizing circadian rhythms.

Key words: high-protein diet; lipid metabolism; circadian rhythm; liver

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