Adult mice are unresponsive to AAV8-Gremlin1 gene therapy targeting the liver.

ABSTRACT:

Objective

Gremlin 1 (GREM1) is a secreted BMP2/4 inhibitor which regulates commitment and differentiation of human adipose precursor cells and prevents the browning effect of BMP4. GREM1 is an insulin antagonist and serum levels are high in type 2 diabetes (T2D). We here examined in vivo effects of AAV8 (Adeno-Associated Viral vectors of serotype eight) GREM 1 targeting the liver in mature mice to increase its systemic secretion and also, in a separate study, injected recombinant GREM 1 intraperitoneally. The objective was to characterize systemic effects of GREM 1 on insulin sensitivity, glucose tolerance, body weight, adipose cell browning and other local tissue effects.

Methods

Adult mice were injected with AAV8 vectors expressing GREM1 in the liver or receiving regular i

SUBMITTER: Khatib Shahidi R 

PROVIDER: S-EPMC7895349 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature