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

Xiaoming Ma, Xing Xue, Jingxin Zhang, Shuang Liang, Chunfang Xu, Yue Wang, Jinzhou Zhu

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2021 Aug

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

Citation

Xiaoming Ma, Xing Xue, Jingxin Zhang, Shuang Liang, Chunfang Xu, Yue Wang, Jinzhou Zhu. Liver Expressed Antimicrobial Peptide 2 is Associated with Steatosis in Mice and Humans. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2021 Aug;129(8):601-610