短期饮食限制对小鼠肝脏胰岛素信号通路与线粒体的影响
Effects of short-term dietary restriction on liver insulin signaling pathway and mi-tochondria in mice
王鑫宇 1刘滢 1隋昕 1姜俊男 1刘涛 1马玉辉 2肖建华1
作者信息
- 1. 东北农业大学动物医学院黑龙江省普通高等学校动物普通疾病防治重点实验室,黑龙江哈尔滨 150030
- 2. 昭苏县西域马业有限责任公司,新疆伊犁 835600
- 折叠
摘要
选用体质量约42 g的昆明小鼠50只,随机分为5组,分别用限时禁食、每日热量限制、隔日禁食、高能量饲料隔日禁食4种饮食限制方法适应性饲养1周后,限制饮食16 d.通过葡萄糖耐受试验观察各组小鼠葡萄糖敏感性情况;对各组小鼠肝脏组织HE染色观察损伤情况;Western blot方法检测肝脏组织各指标的表达情况;免疫荧光化学染色法检测肝脏组织中FOXO1指标的定位情况.结果显示,除了限时禁食组,其他短期饮食限制组均使肝脏肿瘤坏死因子α(TNFα)表达水平与丙二醛(MDA)含量降低,核因子红细胞2相关因子2(NRF2)表达水平增加,B淋巴细胞瘤2关联X蛋白(BAX)、剪切-半胱氨酸蛋白酶蛋白3(cleaved-Caspase-3)、p21、p16的表达水平降低(P＜0.05);4种短期饮食限制方法均使腺苷酸活化蛋白激酶(AMPK)磷酸化增加,另外肉毒碱棕榈酰基转移酶1A(CTP1a)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)、视神经萎缩蛋白1(OPA1)、线粒体融合蛋白2(MFN2)、线粒体膜外的胞质动力相关蛋白1(DRP1)蛋白水平也升高,核内叉头框蛋白1(FOXO1)与葡萄糖转运蛋白载体4(GLUT4)水平下降(P＜0.05).结果表明,短期隔日禁食与每日热量限制使肝脏细胞脂肪的沉积减少,肝脏抗氧化能力增强,炎症、细胞调亡和衰老均减轻;短期饮食限制后,肝脏葡萄糖摄取减少,脂肪酸氧化程度加大,肝脏以脂肪酸为主要的代谢底物;线粒体的融合和分裂均增强,线粒体周转加快;小鼠肝脏胰岛素信号通路敏感性和作用得到增强.
Abstract
Fifty Kunming mice with a body weight of about 42 g were randomly divided into 5 groups.Four dietary restriction methods were used,including time-limited fasting,daily calorie re-striction,alternate day fasting and high-energy feed alternate day fasting,respectively.After one week of adaptive feeding,the diet was restricted for 16 days.The glucose sensitivity of each group of mice was determined through glucose tolerance experiments;the damage of liver tissue in each group of mice was checked by HE staining;Western blot method was used to detect the expression of various indicators in liver tissue;immunofluorescence chemical staining was used to detect the localization of FOXO1 index in liver tissue.The results showed that except for time-limited fasting group,the expression level of tumor necrosis factor(TNFα)and malondialdehyde(MDA)in liver was decreased in all short-term dietary restriction groups,and the expression level of nuclear factor erythroid 2-related factor 2(NRF2)was increased,and the expression levels of BCL-2-associated X protein(BAX),cleaved-Caspase-3,p21,and p16 were decreased(P＜0.05).In addition,four short-term dietary restriction methods all increased AMPK phosphorylation,the levels of carnitine palmitoyl transferase1a(CTP1a),phosphoinositide-3 kinase(PI3K),protein kinase B(AKT),optic atrophy1(OPA1),mitofusin2(MFN2)and dynamin related protein 1(DRP1)were also increased,and the levels of forkhead box protein O1(FOXO1)in the nucleus and glucose transporter4(GLUT4)were decreased(P＜0.05).The results showed that short-term alternate-day fasting and daily caloric restriction reduce liver cell fat deposition,enhance liver antioxidant capacity and allevi-ated inflammation,cell apoptosis and senescence.After short-term dietary restriction,liver glucose intake decreases,fatty acid oxidation increases,and liver takes fatty acid as the main metabolic sub-strate.Mitochondrial fusion and division are enhanced,and mitochondrial turnover is accelerated.The sensitivity and function of mouse liver insulin signaling pathway are enhanced.
关键词
饮食限制/肝脏/胰岛素信号通路/线粒体/小鼠Key words
dietary restriction/liver/insulin signaling pathway/mitochondria/mice引用本文复制引用
出版年
2024
NETL
NSTL
万方数据