Liraglutide suppresses obesity and induces brown fat-like phenotype via Soluble Guanylyl Cyclase mediated pathway in vivo and in vitro.

Strategies for driving white adipose tissue (WAT) to acquire brown-like characteristics are a promising approach to reduce obesity. Liraglutide has been reported to active brown adipose tissue (BAT) thermogenesis and WAT browning by rapid intracerebroventricular injection in mice. In this study, we investigated the effects and possible mechanisms of liraglutide on WAT browning by chronic treatment. Here, we show that liraglutide significantly decreases body weight of mice and reduces the size of white adipocytes. By quantity polymerase chain reaction, immunoblotting analysis, cell immunofluorescence or immunocytochemical staining, we found liraglutide induced WAT browning because it up-regulated lipolytic activity, BAT, as well as mitochondrial marker genes in inguinal and peripheral renal WAT. We also confirmed liraglutide induced browning of 3T3-L1 because it enhanced expression of BAT and mitochondrial specific genes. In further, we observed that, soluble guanylyl cyclase (sGC) and protein kinase G I (PKGI) were up-regulated by liraglutide in vivo and in vitro; stimulation of sGC elevated expression of BAT markers and PKGI, which suggested that liraglutide induced WAT browning via sGC-dependent pathway. Taken together, this study expands our knowledge on the mechanism of liraglutide inducing WAT browning, and provides a theoretical support for clinical usage of liraglutide on obesity treatment.