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Novel effect of glucagon-like peptide-2 for hepatocellular injury in a parenterally fed rat model of short bowel syndrome

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Abstract

Purpose

Short bowel syndrome (SBS) patients require long-term parenteral nutrition following massive bowel resection, which causes intestinal failure-associated liver disease (IFALD). Previous reports have shown that glucagon-like peptide-2 (GLP-2) resulted in the bowel adaptation for SBS. The aim of this study was to evaluate the effect of GLP-2 for IFALD in a parenterally fed rat model.

Methods

Using rat, a catheter was placed in the jugular vein, and 90% small bowel resection (SBR) was performed. Animals were divided into three groups: SBR and total parenteral nutrition (TPN) (SBS/TPN group), SBR and TPN plus GLP-2 at 1 µg/kg/h [SBS/TPN/GLP-2 (low) group], and SBR and TPN plus GLP-2 at 10 µg/kg/h [SBS/TPN/GLP-2 (high) group]. On day 13, the liver was harvested and analyzed by using nonalcoholic fatty liver disease (NAFLD) score.

Results

Histologically, hepatic steatosis in the SBS/TPN group and SBS/TPN/GLP-2 (high) group was observed. Both steatosis and lobular inflammation score in the SBS/TPN/GLP-2 (low) group were significantly lower compared with those in the other two groups (p < 0.05). Active NAFLD score in the SBS/TPN/GLP-2 (low) group was significantly lower compared with that in the SBS/TPN/GLP-2 (high) group (p < 0.01).

Conclusion

Low-dose GLP-2 intravenous administration improves hepatic steatosis of IFALD following in an SBS parenterally fed rat model.

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Acknowledgements

We thank Mr. Brain Quinn for his comments and help with the manuscript. This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS: 19K10485, 19K09150, 19K09078, 19K03084, 19K18061, 19K17304, 19K18032, 18K08578, 18K16262 17K10555, 17K11514, 17K10183, 17K11515, 16K10466, 16K10094, 16K10095, 16K10434, 16H07090) and Grant for the experimental research in the Japanese Society for Parenteral and Enteral Nutrition.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan

    Keisuke Yano, Tatsuru Kaji, Shun Onishi, Seiro Machigashira, Taichiro Nagai, Toshio Harumatsu, Koji Yamada, Waka Yamada, Mitsuru Muto, Kazuhiko Nakame, Motoi Mukai & Satoshi Ieiri

  2. Clinical Training Center, Kagoshima University Hospital, Kagoshima, Japan

    Tatsuru Kaji

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  1. Keisuke Yano
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Correspondence to Satoshi Ieiri.

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Yano, K., Kaji, T., Onishi, S. et al. Novel effect of glucagon-like peptide-2 for hepatocellular injury in a parenterally fed rat model of short bowel syndrome. Pediatr Surg Int 35, 1345–1351 (2019). https://doi.org/10.1007/s00383-019-04560-8

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