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