摘要
目的 利用Ctrp6基因敲除小鼠建立模型解析隔日禁食改善代谢的作用机制。方法 采用3月龄雌性的野生型(WT)小鼠和Ctrp6基因敲除(KO)小鼠进行隔日禁食实验,每种基因型分为两组:自由采食组(WT,n=9;KO,n=12)和隔日禁食组(WT-ADF,n=12;KO-ADF,n=12)。饲养实验持续14 w,期间所有小鼠自由饮水,每日记录采食量,每周称量体重。13 w进行葡萄糖耐受实验和小鼠行为学实验。14 w饲养实验结束后,取血清检测其中脂代谢相关因子含量,取小鼠皮下脂肪和棕色脂肪组织用RT-PCR检测其中棕脂标志性基因表达,利用蛋白印迹分析相关信号通路。结果 与自由采食组相比,隔日禁食组的WT和KO鼠的累积采食量均降低,体重增加减缓,体脂积累减少,葡萄糖耐受性增加,血脂降低,代谢得到改善。对皮下脂肪的基因表达分析,隔日禁食导致两种基因型小鼠皮下脂肪组织中的白色脂肪棕色化标志基因Ucp1和Pgc1α的mRNA和蛋白丰度均升高,其中KO鼠上升幅度更大;利用蛋白印记分析相关信号通路,隔日禁食组PKA磷酸化水平显著升高。结论 隔日禁食能够减缓小鼠体重增加,减少白色脂肪积累,改善小鼠代谢,这可能与白色脂肪组织中的PKA通路激活,促使UCP1表达上调进而引起小鼠白色脂肪棕色化有关。[营养学报,2022,44(2):173-181]
Objective To explore the alternate-day fasting effects on the improvement of metabolism in CTRP6 gene knockout mice. Methods Three-month-old female wild-type(WT) and CTRP6 knockout(KO) mice were randomly divided into two groups for alternate-day fasting. The ad libitum group(WT, n=9;KO, n=12) and alternate-day fasting group(WT-ADF, n=12;KO-ADF, n=12) were included. The feeding experiment lasted for 14 weeks, during which all mice were free to drinking water, daily feed intake was recorded, and body weight was weighed weekly. Glucose tolerance experiment and behavior experiment were performed at the 13th week. After the 14-week feeding experiment, the serum was taken to detect the content of lipid metabolism-related factors, and the subcutaneous fats and brown adipose tissues were taken to detect the expression of brown fat marker genes by RT-PCR, and the related signal pathways were analyzed by Western blot.Results Compared with the ad libitum group, the cumulative feed intake of WT and KO mice in the alternate-day fasting group were reduced, weight gain was retarded, body fat accumulation was decreased, glucose tolerance was increased and blood lipids was reduced. Gene expression analysis showed that the marker genes of white adipose browning UCP1 and PGC1α were upregulated at both mRNA and protein levels in the subcutaneous fats of mice with both genotypes after alternate-day fasting, in which the increased fold was much higher in KO mice than WT mice. The signaling pathway of PKA exhibited higher phosphorylation level in the alternate-day fasting group. Conclusion Alternate-day fasting can slow down weight gain, reduce the accumulation of white fats, and improve metabolism in mice. This is related to the activation of the PKA pathway and the upregulation of UCP1 in white adipose tissues, which results in the browning of white adipose tissue in mice. [ACTA NUTRIMENTA SINICA, 2022, 44(2):173-181]
作者
黄鑫
郑诚
江祖荣
陈树欣
彭永佳
张瑾
HUANG Xin;ZHENG Cheng;JIANG Zu-rong;CHEN Shu-xin;PENG Yong-jia;ZHANG Jin(College of Agronomy and Biotechnology,Hebei Normal University of Science&Technology,Qinhuangdao 066000;College of Biological,Chemical Sciences and Engineering,Jiaxing University,Jiaxing 314000;Shanghai Drugfarm Biological Technology Co.,Ltd,Shanghai 200437,China)
出处
《营养学报》
CAS
CSCD
北大核心
2022年第2期173-181,共9页
Acta Nutrimenta Sinica
基金
浙江省自然科学基金项目(No.lY20C170003,No lQ18C170002)
嘉兴学院校级重点SRT计划项目(No.CD8517203275)。
关键词
隔日禁食
CTRP6
脂肪积累
白色脂肪棕色化
alternate-day fasting
CTRP6
fat accumulation
browning of white adipose tissue
