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).

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.

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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