Development of brown fat-enriched secreted factor Nrg4-based biologics in the treatment of obesity-associated disorders

Abstract

Type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are two global leading severe diseases which increasingly threaten people’s life and cause great burdens in medical care services. Till now, there is no optimal remedy which can completely cure these diseases. Based on such situation, develop new pharmaceutical therapies as well as identify effective biomarkers for these diseases already come to the top priority for current lab research discovery. Adipokine is believed to play an important role in metabolic dysfunction, thus, it is selected as a modern therapeutic target to solve health disorders. Neuregulin 4 (Nrg4) is a kind of novel adipokine which express mainly in adipose tissue and liver from healthy human and mouse. The reduction of Nrg4 indicates the suffering of metabolic disorder. In this project, recombinant adeno-associated virus serotype 2/8 (rAAV2/8-LSP-hNrg4) was synthesized and applied to over-express human Nrg4 in mouse for in vivo experiments. According to quantitative PCR data, the aim is achieved as rAAV-2/8-LSP-hNrg4 is successfully over-expressing adipokine hNrg4 in mouse.