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

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