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Animal Models

Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis

International Journal of Obesity volume 42, pages 1471–1479 (2018)Cite this article

Subjects

Abstract

Background/Objectives

Obesity is an independent risk factor for severe acute pancreatitis (AP). Leptin plays an important role in energy homeostasis. It has been reported that leptin might also participate in the regulation of the intestinal mucosal barrier and inflammatory response. This study aimed to evaluate the effects of leptin on the intestinal mucosal barrier and inflammatory injury in obese mice with AP.

Subjects/Methods

AP was induced in leptin-deficient (ob/ob) or wild type (WT) mice by peritoneal injection of caerulein. The animals were divided into 4 groups: WT mice with or without exogenous leptin injection and ob/ob mice with or without leptin treatment. The inflammatory scoring of the pancreas and intestine were evaluated. Intestinal permeability, ileal interleukin (IL)-6 and IL-1β, proliferation, apoptosis and intestinal expression levels of claudin-1 and occludin were measured.

Results

Pancreatic pathologic scores (8.50 ± 0.96 vs. 3.78 ± 1.35, p < 0.001), pancreatic levels of IL-6 (8.34 ± 3.21 ng/mg vs. 4.99 ± 0.53 ng/mg, p = 0.022), intestinal oedema scores (2.25 ± 0.46 vs. 1.14 ± 0.69, p = 0.001) and intestinal permeability to FD4 (0.78 ± 0.06 μg/ml vs. 0.53 ± 0.11 μg/ml, p < 0.001) were significantly higher in ob/ob mice than those in WT mice. Leptin replacement in ob/ob mice greatly improved the intestinal permeability (FD4 0.66 ± 0.03 μg/ml, vs. 0.78 ± 0.06 μg/ml, p = 0.012), increased the ileal expression of claudin-1(1.07 ± 0.08 vs. 0.83 ± 0.07 relative densitometry, p = 0.001) and reduced intestinal IL-6 and IL-1β to levels comparable to those in WT mice. The pancreatic level of IL-6 in ob/ob mice treated with leptin was also significantly decreased relative to that of untreated ob/ob mice (4.45 ± 1.71 ng/mg vs. 8.34 ± 3.21 ng/mg, p = 0.010).

Conclusions

Obesity may aggravate intestinal inflammation and increase intestinal permeability under the condition of acute pancreatitis. Exogenous leptin supplementation was in favour of anti-inflammation and improvement of intestinal mucosal barrier.

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Acknowledgements

This study was supported by the Natural Science Foundation of China (NSFC, 81300359, 81401949, U1702281, 81200285 and 81670551), Chinesisch-Deutsches Zentrum für Wissenschaftsförderung (GZ1065), The Science and Technology Support Program of Sichuan Province (2016SZ0041) and by the National Key R&D Program of China (2017YFA0205400). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of this manuscript. We would like to thank Associate Professor Rui Liu, technician Chong Zhao from the Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University; intermediate technician Sisi Wu, and technicians Yu Ding, Xuemei Chen and Guonian Zhu from the Core Facility, West China Hospital, Sichuan University, for their technical assistance.

Funding

This study was funded by the Natural Science Foundation of China (NSFC, 81300359, 81401949, U1702281, 81200285 and 81670551), Chinesisch-Deutsches Zentrum für Wissenschaftsförderung (GZ1065), the National Key R&D Program of China (2017YFA0205400), and The Science and Technology Support Program of Sichuan Province (2016SZ0041). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of this manuscript.

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Author notes

  1. These authors contributed equally: Cheng Ye, Rui Wang.

Authors and Affiliations

  1. Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China

    Cheng Ye, Rui Wang, Zhiyin Huang & Chengwei Tang

  2. Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

    Cheng Ye, Rui Wang, Zhiyin Huang & Chengwei Tang

  3. Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China

    Mojin Wang

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Correspondence to Chengwei Tang.

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Ye, C., Wang, R., Wang, M. et al. Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis. Int J Obes 42, 1471–1479 (2018). https://doi.org/10.1038/s41366-018-0125-y

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