研究论文 RESEARCH PAPER

高脂饲粮对小鼠摄食节律与肝脏核心时钟蛋白表达的影响

  • 罗佳 ,
  • 闫征 ,
  • 李胜涛 ,
  • 卢卓恒 ,
  • 章浩月 ,
  • 徐丽萍 ,
  • 王欣
展开
  • 宁波大学医学院, 宁波 315211
罗佳(1997-),女,四川遂宁人,硕士研究生,研究方向为基础营养与代谢病。E-mail:luojia2636@163.com

收稿日期: 2021-07-29

  网络出版日期: 2022-03-14

基金资助

浙江省基础公益技术研究计划(LGD19H070001,LY20H030001);宁波市社会公益研究计划项目(202002N3160)

Effects of High-Fat Diet on Feeding Rhythm and Expression of Hepatic Core Clock Proteins in Mice

  • LUO Jia ,
  • YAN Zheng ,
  • LI Shengtao ,
  • LU Zhuoheng ,
  • ZHANG Haoyue ,
  • XU Liping ,
  • WANG Xin
Expand
  • School of Medicine, Ningbo University, Ningbo 315211, China

Received date: 2021-07-29

  Online published: 2022-03-14

摘要

本试验旨在以小鼠为模型探究摄食节律在高脂饲粮(HFD)诱导的代谢综合征(MS)中的作用。将健康的雄性小鼠分为4组,每组5只,连续3个月分别给予含4%脂肪的普通饲粮(Con组)和含10%(10% HFD组)、45%(45% HFD组)、60%(60% HFD组)脂肪的HFD,每周记录小鼠体重,收集血清、肝脏等标本检测生物标志物。为了进一步探究HFD对摄食节律的作用,将另一批小鼠分为Con组与45% HFD组,第1周2组小鼠均饲喂普通饲粮,第2周和第3周Con组继续饲喂普通饲粮,HFD组则饲喂含45%脂肪的HFD,每周记录3 d夜昼摄食量,3周后脱颈处死,取肝脏组织分析核心时钟蛋白CLOCK和BMAL1的表达变化。结果显示:与其他各组比较,45% HFD组小鼠体重增加最快;与Con组相比,45% HFD组小鼠肝脏甘油三酯(TG)、总胆固醇(TC)含量显著升高(P<0.05),并出现显著糖耐量损害,病理切片可见肝脏脂肪变性。与Con组比较,10% HFD组、45% HFD组和60% HFD组肝脏CLOCK的蛋白表达量明显减弱,然而核心时钟基因ClockBmal1的mRNA表达量在各组之间无显著差异(P>0.05)。与Con组比较,45% HFD组小鼠日间摄食量增多,而夜间摄食量减少,摄食行为节律被抑制,且肝脏CLOCK的蛋白表达量显著下调(P<0.05),而肝脏BMAL1的蛋白表达量则无显著变化(P>0.05)。综上可知,当HFD脂肪含量为45%时,其诱导小鼠MS的作用最强;HFD抑制小鼠摄食节律,而摄食节律改变可能与肝脏CLOCK表达下调密切相关。

本文引用格式

罗佳 , 闫征 , 李胜涛 , 卢卓恒 , 章浩月 , 徐丽萍 , 王欣 . 高脂饲粮对小鼠摄食节律与肝脏核心时钟蛋白表达的影响[J]. 动物营养学报, 2022 , 34(3) : 1955 -1962 . DOI: 10.3969/j.issn.1006-267x.2022.03.054

Abstract

This study was conducted to explore the effect of feeding rhythm on the metabolic syndrome (MS) induced by high-fat diet (HFD) using mouse model. Healthy male mice were divided into 4 groups with 5 mice per group, and mice in the 4 groups were fed a normal diet containing 4% fat (Con group) and three HFD containing 10% (10%HFD group), 45% (45%HFD group) and 60% (60%HFD group) fat for 3 months, respectively. The body weight was recorded every week. The serum and liver tissues were collected to detect biomarkers. In order to validate the effect of HFD on feeding rhythm, a second batch of mice were divided into Con group and 45%HFD group. In the first week, mice in the two groups were fed the normal diet. During the second and third weeks, mice in the Con group continue to fed the normal diet, but mice in the 45%HFD group were fed the HFD containing 45% fat. Diet consumption during night and day time was recorded for 3 days a week. Three weeks later, the mice were sacrificed and the liver tissues were collected for the analysis of expression changes of core clock proteins CLOCK and BMAL1. The results showed as follows:mice in the 45%HFD group gained the most body weight among all groups. Compared with the Con group, the contents of liver triglyceride (TG) and total cholesterol (TC) in the 45%HFD group were significantly decreased (P<0.05), the glucose tolerance showed abnormal phenomenon, and the pathological section showed liver steatosis. Compared with the Con group, the protein expression level of CLOCK in liver in the 10%HFD group, 45%HFD group and 60%HFD group was obviously decreased, while the mRNA expression levels of core clock genes Clock and Bmal1 had no significant differences among groups (P>0.05). Compared with the Con group, mice in the 45%HFD group increased daytime feed intake and increased nighttime feed intake, the diet consumption rhythm was inhibited. And again, the protein expression level of CLOCK in liver was significantly decreased by 45%HFD treatment (P<0.05), while the protein expression level of BMAL1 in liver had no significant change (P>0.05). In conclusion, HFD containing 45% fat is the strongest in inducing MS in mouse. Feeding rhythm is inhibited by HFD, which may be closely related to the down-regulation of liver CLOCK expression.

参考文献

[1] SAKLAYEN M G.The global epidemic of the metabolic syndrome[J].Current Hypertension Reports,2018,20(2):12.
[2] PEREIRA M A,KARTASHOV A I,EBBELING C B,et al.Fast-food habits,weight gain,and insulin resistance (the CARDIA study):15-year prospective analysis[J].Lancet,2005,365(9453):36-42.  
[3] HUANG W Y,RAMSEY K M,MARCHEVA B,et al.Circadian rhythms,sleep,and metabolism[J].The Journal of Clinical Investigation,2011,121(6):2133-2141.  
[4] ZIMMET P,ALBERTI K G M M,STERN N,et al.The circadian syndrome:is the metabolic syndrome and much more![J].Journal of Internal Medicine,2019,286(2):181-191.  
[5] GEKAKIS N,STAKNIS D,NGUYEN H B,et al.Role of the CLOCK protein in the mammalian circadian mechanism[J].Science,1998,280(5369):1564-1569.  
[6] LI D Y,IKAGA R,OGAWA H,et al.Different expressions of clock genes in fatty liver induced by high-sucrose and high-fat diets[J].Chronobiology International,2021,38(5):762-778.  
[7] KOHSAKA A,LAPOSKY A D,RAMSEY K M,et al.High-fat diet disrupts behavioral and molecular circadian rhythms in mice[J].Cell Metabolism,2007,6(5):414-421.  
[8] YANAGIHARA H,ANDO H,HAYASHI Y,et al.High-fat feeding exerts minimal effects on rhythmic mRNA expression of clock genes in mouse peripheral tissues[J].Chronobiology International,2006,23(5):905-914.  
[9] LIAN C Y,ZHAI Z Z,LI Z F,et al.High fat diet-triggered non-alcoholic fatty liver disease:a review of proposed mechanisms[J].Chemico-Biological Interactions,2020,330:109199.
[10] JIANG P R,ZHENG W Y,SUN X N,et al.Sulfated polysaccharides from Undaria pinnatifida improved high fat diet-induced metabolic syndrome,gut microbiota dysbiosis and inflammation in BALB/c mice[J].International Journal of Biological Macromolecules,2021,167:1587-1597.
[11] MORENO-FERNÁNDEZ S,GARCÉS-RIMÓN M,VERA G,et al.High fat/high glucose diet induces metabolic syndrome in an experimental rat model[J].Nutrients,2018,10(10):1502.
[12] KHANNA S,WALIA S,KONDEPUDI K K,et al.Administration of indigenous probiotics modulate high-fat diet-induced metabolic syndrome in Sprague Dawley rats[J].Antonie van Leeuwenhoek,2020,113(9):1345-1359.  
[13] POTTER G D M,CADE J E,GRANT P J,et al.Nutrition and the circadian system[J].The British Journal of Nutrition,2016,116(3):434-442.  
[14] JANG H,LEE G,KONG J,et al.Feeding period restriction alters the expression of peripheral circadian rhythm genes without changing body weight in mice[J].PLoS One,2012,7(11):e49993.
[15] HATORI M,VOLLMERS C,ZARRINPAR A,et al.Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet[J].Cell Metabolism,2012,15(6):848-860.  
[16] PIVOVAROVA O,JVRCHOTT K,RUDOVICH N,et al.Changes of dietary fat and carbohydrate content alter central and peripheral clock in humans[J].The Journal of Clinical Endocrinology and Metabolism,2015,100(6):2291-2302.  
[17] SHI D M,CHEN J,WANG J F,et al.Circadian clock genes in the metabolism of non-alcoholic fatty liver disease[J].Frontiers in Physiology,2019,10:423.
[18] TUREK F W,JOSHU C,KOHSAKA A,et al.Obesity and metabolic syndrome in circadian clock mutant mice[J].Science,2005,308(5724):1043-1045.  
[19] LANDGRAF D,NEUMANN A M,OSTER H.Circadian clock-gastrointestinal peptide interaction in peripheral tissues and the brain[J].Best Practice & Research.Clinical Endocrinology & Metabolism,2017,31(6):561-571.  
[20] STORCH K F,PAZ C,SIGNOROVITCH J,et al.Intrinsic circadian clock of the mammalian retina:importance for retinal processing of visual information[J].Cell,2007,130(4):730-741.  
文章导航

/