Recombinant Human GLP-1 Beinaglutide Regulates Lipid Metabolism of Adipose Tissues in Diet-Induced Obese Mice

Abstract

GLP-1 analogs are a novel class of injectable glucose-lowering agents with benefits of weight loss and improved cardiovascular outcomes. Adipose tissues are important regulators of lipid metabolism, but the role of GLP-1 in lipid metabolism of adipose tissues remains to be elucidated. The aim of this study was to determine the action of recombinant human GLP-1 (rhGLP-1) Beinaglutide (BN) in the insulin sensitivity and lipid metabolism of adipose tissues. We have shown that, after 6 weeks of BN treatment, high fat diet (HFD) induced obese mice displayed lower body weight, fat mass, and serum lipid levels. In addition, BN promoted the activity of insulin signaling in the white adipose tissues (WAT) in vivo and in vitro. Furthermore, by applying mass spectrometry-based lipidomic assay combined with RNA sequencing (RNA-seq), we have found that the BN treatment caused significant changes in content and composition of different lipid classes, including glycerolipids, glycerophospholipids and sphingolipids, as well as expression of genes in lipid metabolic pathways in the adipose tissues, particular in the subcutaneous WAT. Taken together, our data demonstrate that rhGLP-1 BN could resist HFD-induced obesity and lipid storage by targeting the composition of major lipid classes and the expression of genes in lipid metabolism of adipose tissues.