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Exp Clin Endocrinol Diabetes 2021; 129(08): 601-610
DOI: 10.1055/a-1210-2357
Article

Liver Expressed Antimicrobial Peptide 2 is Associated with Steatosis in Mice and Humans

Xiaoming Ma‡
1   Department of General Surgery, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China
,
Xing Xue‡
2   Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
,
Jingxin Zhang
3   Department of General Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
,
Shuang Liang
4   Medical School of Nantong University, Nantong 226001, Jiangsu, China
,
Chunfang Xu
5   Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
,
Yue Wang
6   Department of Hepatology, The Fifth People’s Hospital of Suzhou, Suzhou, China
,
Jinzhou Zhu
5   Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
› Author Affiliations Funding This work was supported by the Youth Program of Suzhou Health Committee (KJXW2019001) and Jiangsu Provincial Key Development Program (BE2018659).
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Abstract

Background and Aims Liver expressed antimicrobial peptide 2 (LEAP2) is recently identified as a regulator in energy metabolism. This study aims to 1) investigate the role of leap2 in hepatic steatosis in C57BL/6 mice; 2) evaluate the association between circulating LEAP2 levels and liver fat contents in a hospital based case-control study.

Methods The rodent experiment: western blotting and qPCR were performed to evaluate leap2 levels, lipid metabolism pathways and insulin signaling. shRNA was used to knockdown leap2. The clinical study: commercial ELISA kits were used to measure circulating LEAP2 levels (validated by western blotting). Liver fat content was estimated using MRI-derived proton density fat fraction and FibroScan-derived controlled attenuation parameter.

Results The rodent experiment found the hepatic expression and secreted levels of leap2 were increased in mice with diet-induced steatosis. Leap2 knockdown ameliorated steatosis via lipolytic/lipogenic pathway and improved insulin sensitivity via IRS/AKT signaling. The clinical study reported increased circulating levels of LEAP2 in the subjects with steatosis. Moreover, LEAP2 correlated positively with age, body mass index, waist-to-hip ratio, liver fat content, fasting insulin and HOMA-IR, whereas inversely with acyl-ghrelin. Furthermore, the circulating levels of LEAP2 are dependent on liver fat content, acyl-ghrelin and fasting glucose. Lastly, circulating LEAP2 is an independent predictor of NAFLD.

Conclusions The study suggests LEAP2 is associated with hepatic steatosis, which may involve lipolytic/lipogenic pathway and insulin signaling.

Key words

controlled attenuation parameter - liver expressed antimicrobial peptide 2 - magnetic resonance imaging - nonalcoholic fatty liver disease - proton density fat fraction

Supplementary Material



Publication History

Received: 05 May 2020
Received: 13 June 2020

Accepted: 30 June 2020

Article published online:
15 September 2020

© 2020. Thieme. All rights reserved.

© Georg Thieme Verlag KG
Stuttgart · New York

 

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