GLP-2 Prevents Intestinal Mucosal Atrophy and Improves Tissue Antioxidant Capacity in a Mouse Model of Total Parenteral Nutrition.

Qiucheng Lei,Xiao Wan,Huijun Zheng,Tingting Jiang,Chao Wu,Xinying Wang,Jingcheng Bi,Xuejin Gao,Feng Tian

doi:10.3390/nu8010033

Abstract

We investigated the effects of exogenous glucagon-like peptide-2 (GLP-2) on mucosal atrophy and intestinal antioxidant capacity in a mouse model of total parenteral nutrition (TPN). Male mice (6–8 weeks old) were divided into three groups (n = 8 for each group): a control group fed a standard laboratory chow diet, and experimental TPN (received standard TPN solution) and TPN + GLP-2 groups (received TPN supplemented with 60 µg/day of GLP-2 for 5 days). Mice in the TPN group had lower body weight and reduced intestinal length, villus height, and crypt depth compared to the control group (all p < 0.05). GLP-2 supplementation increased all parameters compared to TPN only (all p < 0.05). Intestinal total superoxide dismutase activity and reduced-glutathione level in the TPN + GLP-2 group were also higher relative to the TPN group (all p < 0.05). GLP-2 administration significantly upregulated proliferating cell nuclear antigen expression and increased glucose-regulated protein (GRP78) abundance. Compared with the control and TPN + GLP-2 groups, intestinal cleaved caspase-3 was increased in the TPN group (all p < 0.05). This study shows GLP-2 reduces TPN-associated intestinal atrophy and improves tissue antioxidant capacity. This effect may be dependent on enhanced epithelial cell proliferation, reduced apoptosis, and upregulated GRP78 expression.

Highlights

Total parenteral nutrition (TPN) is a critical therapeutic modality for patients with impaired gut function, such as patients with short bowel syndrome, severe inflammatory bowel disease, or chronic idiopathic intestinal pseudo-obstruction [1,2,3]
Long-term total parenteral nutrition (TPN) can lead to reduced epithelial cell (EC) proliferation, increased EC apoptosis and mucosal atrophy [6,7], all of which may contribute to an associated increase in risk of infectious complications [8,9]
Weight nor weight gain of mice was affected by TPN and glucagon-like peptide-2 (GLP-2)

Summary

Introduction

Total parenteral nutrition (TPN) is a critical therapeutic modality for patients with impaired gut function, such as patients with short bowel syndrome, severe inflammatory bowel disease, or chronic idiopathic intestinal pseudo-obstruction [1,2,3]. Almost 400,000 patients per year in the United States were dependent on TPN or intravenous feeding care for survival [5]. Long-term TPN can lead to reduced epithelial cell (EC) proliferation, increased EC apoptosis and mucosal atrophy [6,7], all of which may contribute to an associated increase in risk of infectious complications [8,9]. TPN-associated intestinal hypoplasia and epithelial cell injury were strongly linked to gut barrier dysfunction [10] and increased bacterial translocation [11]. The potential mechanisms contributing to TPN-associated intestinal atrophy and epithelial cell injury remain poorly understood.

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Discussion

Conclusion