Role of gut microbiota in attenuating the effect of orlistat on pancreatic exocrine function in mice
10.3760/cma.j.cn115667-20240510-00093
- VernacularTitle:小鼠肠道菌群在奥利司他对胰腺外分泌功能影响中的作用
- Author:
Fengping SUN
1
;
Feng ZHANG
;
Yongwei FENG
;
Hong CAO
Author Information
1. 江南大学附属医院营养科，无锡 214122
- Publication Type:Journal Article
- Keywords:
Pancreas;
High fat diet;
Intestinal flora;
Orlistat;
Mice
- From:
Chinese Journal of Pancreatology
2025;25(3):211-216
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of the gut microbiota in the effect of orlistat on pancreatic exocrine function in mice.Methods:Sixty male C57BL/6J mice were divided into normal drinking water group and antibiotic group by using random number table method. In antibiotic group, vancomycin hydrochloride 0.5 g/L, ampicillin sodium 1 g/L, neomycin sulfate 1 g/L and metronidazole 1 g/L were added to the drinking water, which were administrated in combination for 2 weeks. The normal drinking water group and the antibiotic group were fed by normal diet (ND group, AND group), high-starch diet (HSD group, AHSD group), and high-fat diet (HFD group, AHFD group), respectively. The six groups were then gavaged with orlistat (O, 50 mg/kg) twice a day on the basis of the same diet, and were designated as ND+O group, AND+O group, HSD+O group, AHSD+O group, HFD+O group and AHFD+O group. The corresponding control groups were gavaged with the same amount of sterilized water, and the antibiotic group continued to drink antibiotic water. The intervention lasted for 12 weeks. Body weight and pancreatic weight were measured and recorded, and the pancreatic-to-body weight ratio was calculated. Blood samples were collected for the detection of inflammatory factor IL-6 and TNF α by ELISA. Pancreatic tissues were harvested for hematoxylin-eosin staining and subsequent pathological evaluation. Proteins were extracted from pancreatic tissues, and Western blot analysis was performed to detect the expression levels of pancreatic lipase and amylase.Results:In condition of normal diet and high fat diet, the body weights in the HFD group, HFD+O group, AHFD group [(37.22±4.49), (32.36±1.12), (33.64±2.52)g], were higher than that of ND group, ND+O group and AND group [(29.46±2.48), (27.48±1.98), (24.78±1.50)g], respectively; while the body weight of HFD+O group and AHFD+O group[(32.36±1.12), (27.82±0.61)g] were greatly lower than that of HFD group and AHFD group [(37.22±4.49), (33.64±2.52)g], respectively and body weight of ANFD+O group decreased to the level of normal diet group. In condition of normal diet, high fat diet and high starch diet, the pancreatic weight/body weight ratio was significantly higher in ND+O group (7.51±1.51)mg/g than ND group (5.19±1.06)mg/g, in HSD+O group and AHSD+O group [(6.68±0.34), (6.80±0.72)mg/g] higher than HSD group (4.37±0.91), in HFD+O group and AHFD+O group [(6.43±0.20), (6.67±0.53)mg/g] higher than HFD group (4.58±0.42)mg/g. The pancreatic acinar cells in mice from the ND+O, AND, AND+O, HSD+O, AHSD, AHSD+O, HFD+O, AHFD, and AHFD+O groups had significantly higher density of zymogen granules and exhibited larger eosinophilic stained area. The expression of pancreatic lipase was higher in AND+O group (1.96±0.39) than ND group and ND+O group [(1.00±0.28), (1.16±0.49)], in AHSD+O group (1.70±0.36) than HSD group (0.83±0.15), in AHFD+O group (1.71±0.45) than HFD group and HFD+O group [(0.89±0.23), (0.98±0.17)]. All the differences above were statistically significant (all P values <0.05). Conclusions:The gut microbiota can reduce the damage of orlistat to exocrine function of the pancreas and has a protective effect on the exocrine function of the pancreas.
