Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.931
Peer-review started: June 15, 2020
First decision: June 20, 2020
Revised: July 23, 2020
Accepted: September 15, 2020
Article in press: September 15, 2020
Published online: November 27, 2020
Processing time: 161 Days and 18.5 Hours
Current standard of care for non-alcoholic fatty liver disease (NAFLD) patients varies according to disease stage, but includes lifestyle interventions common insulin sensitizers, antioxidants and lipid modifiers. However, to date specific therapies for have shown little histological or fibrosis stage improvement in large clinical trials and there is still no licensed therapy for NAFLD. Given the high prevalence, limited treatment options and significant screening costs for the general population, new treatments are urgently required.
Vascular adhesion protein-1 (VAP-1) is an enzyme with proven contributions to systemic and hepatic glucose handling, inflammation and fibrosis. We now show an additional role in hepatic steatosis.
In the current investigation, we aimed to assess the potential for inhibition of the amine oxidase enzyme VAP-1 to modify hepatic lipid accumulation in NAFLD.
We have used a combination of human cell cultures, a murine model and human precision cut liver slices to understand the contribution of the semicarbazide sensitive amine oxidase enzyme VAP-1 to lipid handling in NAFLD. This molecule is of increasing therapeutic interest due to its ability to regulate hepatic inflammation and fibrosis.
VAP-1 increases lipid accumulation and reduces triglyceride export by hepatocytes. This is linked to alterations in expression of key lipid transporters including FABP1, 2 and 4, FATP2-5 and LRP1 and key regulators such as PPARα. In agreement, VAP-1 deficient mice are protected against steatosis on high fat diet.
We suggest the multifaceted effects of VAP-1 within the liver in NAFLD make it an interesting target for pharmacological intervention.
We would argue that the increased pharmaceutical interest in amine oxidase inhibitors is well placed.