Effect of maternal high fat diet on intestinal barrier function in early life of offspring mice

Q4 Nursing

中华临床营养杂志 Pub Date : 2018-12-30 DOI:10.3760/CMA.J.ISSN.1674-635X.2018.06.007

Runxiang Xie, H. Cao, Xinyuan Huang, Tianyu Liu, Sinan Wang, Wenxiao Dong

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引用次数: 1

Abstract

Objective To observe the effects of maternal high fat diet (MHFD) during pregnancy and lactation on intestinal barrier function in offspring mice. Methods C57BL/6 pregnant mice were divided into high fat diet (MHFD) group and normal diet group (MND) randomly and were given high fat diet and normal diet during pregnancy (3 weeks) and lactation (3 weeks) respectively. Both groups of offspring mice were naturally given and bodyweight of pups was monitored at birth and weekly. After weaning, the intestinal permeability of offspring mice was detected by fluorescein isothiocyanate conjugated-dextran method (FITC-D). Immunofluorescence was used to detect the expression of ZO-1 in intestinal tissues. HE staining was used to assess the villus length and crypt depth. The intestinal cell proliferation(expression of Ki-67)and Mucin 2(MUC2) were assessed by immunohistochemistry. PAS staining was used to evaluate the goblet cells. The expression of inflammatory cytokines including IL-1β, IL-6, and TNF-α in intestinal tissue were measured by real-time PCR. Results At the age of 2 and 3 weeks, the offspring in MHFD group were significantly heavier than those in MND group. HE staining showed no obvious microscopic inflammation in both groups of 3 weeks old offspring mice, however, the relative expression levels of IL-1β (1.95±0.53 vs. 1.13±0.15; t=3.65, P=0.005), IL-6(1.40±0.71 vs. 0.73±0.17; t=2.72, P=0.04), and TNF-α(1.63±0.53 vs. 1.04±0.12; t=2.64, P=0.02) mRNA were significantly higher in the MHFD group. Compared with the 3 weeks old offspring mice in MND group, MHFD significantly increased the permeability of intestine and decreased the expression of ZO-1 in membrane. The number of Ki-67 positive cells (18.00±4.74 vs. 24.60±4.17; t=3.31, P=0.004) in each villus, goblet cells (14.70±2.91 vs. 28.10±4.95; t=7.38, P<0.001) and MUC2 positive cells (20.60±3.13 vs. 30.00±3.33; t=6.50, P<0.001) in each crypt were significantly lower than those in MND group. Conclusion Maternal high fat diet in early life of offspring mice can induce intestinal low grade inflammation and lead to the disruption of intestinal mucosal barrier in offspring mice, which may be involved in the progeny diseases. Key words: Early life; High fat diet; Inflammation; Intestinal mucosal barrier

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母体高脂饮食对子代小鼠早期肠道屏障功能的影响

目的观察妊娠期和哺乳期母体高脂饮食（MHFD）对仔鼠肠道屏障功能的影响。方法将C57BL/6妊娠小鼠随机分为高脂饮食组（MHFD）和正常饮食组（MND），分别在妊娠期（3周）和哺乳期（3周）给予高脂饮食和正常饮食。这两组后代小鼠都是自然喂养的，并在出生时和每周监测幼崽的体重。断奶后，用异硫氰酸荧光素-葡聚糖偶联法（FITC-D）检测后代小鼠的肠道通透性。免疫荧光法检测ZO-1在肠组织中的表达。HE染色用于评估绒毛长度和隐窝深度。肠细胞增殖（Ki-67的表达）和粘蛋白2（MUC2）通过免疫组织化学评估。PAS染色用于评估杯状细胞。实时PCR检测肠组织中炎性细胞因子IL-1β、IL-6和TNF-α的表达。结果在2周龄和3周龄时，MHFD组的后代明显重于MND组。HE染色显示，两组3周龄后代小鼠均未出现明显的显微镜下炎症，但MHFD组IL-1β（1.95±0.53 vs.1.13±0.15；t=3.65，P=0.005）、IL-6（1.40±0.71 vs.0.73±0.17；t=2.72，P=0.04）和TNF-α（1.63±0.53 vs 1.04±0.12；t=2.64，P=0.02）mRNA的相对表达水平显著升高。与MND组的3周龄后代小鼠相比，MHFD显著增加了肠道通透性，降低了ZO-1在膜中的表达。每个绒毛中Ki-67阳性细胞的数量（18.00±4.74 vs.24.60±4.17；t=3.31，P=0.004）、杯状细胞（14.70±2.91 vs.28.10±4.95；t=7.38，P<0.001）和MUC2阳性细胞的数目（20.60±3.13 vs.30.00±3.33；t=6.50，P=0.001）显著低于MND组。结论母本高脂饮食可诱发子代小鼠肠道低度炎症，破坏子代小鼠的肠黏膜屏障，可能与子代疾病有关。关键词：早期生活；高脂肪饮食；炎症；肠粘膜屏障

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来源期刊

中华临床营养杂志 Nursing-Nutrition and Dietetics

CiteScore

0.20

自引率

0.00%

发文量

2282

期刊介绍： The Chinese Journal of Clinical Nutrition was founded in 1993. It is the first professional academic journal (bimonthly) in my country co-sponsored by the Chinese Medical Association and the Chinese Academy of Medical Sciences to disseminate information on clinical nutrition support, nutrient metabolism, the impact of nutrition support on outcomes and "cost-effectiveness", as well as translational medicine and nutrition research. It is also a professional journal of the Chinese Medical Association's Parenteral and Enteral Nutrition Branch. The purpose of the Chinese Journal of Clinical Nutrition is to promote the rapid dissemination of knowledge on nutrient metabolism and the rational application of parenteral and enteral nutrition, focusing on the combination of multidisciplinary and multi-regional field investigations and clinical research. It mainly reports on nutritional risk screening related to the indications of parenteral and enteral nutrition support, "cost-effectiveness" research on nutritional drugs, consensus on clinical nutrition, guidelines, expert reviews, randomized controlled studies, cohort studies, glycoprotein and other nutrient metabolism research, systematic evaluation of clinical research, evidence-based case reports, special reviews, case reports and clinical experience exchanges, etc., and has a special column on new technologies related to the field of clinical nutrition and their clinical applications.