Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

Abstract

AbstractLiraglutide (LRG), one agonist of glucagon-like peptide-1, has multiple lipid-lowering effects in type 2 diabetes mellitus, however, studies on the role of LRG in saturated fatty acid-induced bone loss are limited. Therefore, our aim was to investigate whether LRG reduces palmitate (PA)-induced apoptosis and whether the mechanism involves PKA/β-catenin/Bcl-2/Bax in osteoblastic MC3T3-E1 cells. MC3T3-E1 cells were treated with different concentrations of PA, LRG, or pretreated with Exendin 9–39 and H89, cell viability, intracellular reactive oxygen species (ROS) and cAMP levels, apoptosis and the expression of protein kinase A (PKA), β-catenin, cleaved-Capase 3, Bcl2-Associated X Protein (Bax) and B-cell lymphoma-2 (Bcl-2) along with expression of Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were evaluated. PA treatment inhibited cell proliferation and cAMP levels, elevated intracellular ROS levels and promoted apoptosis, increased protein expressions of RANKL, Bax and Cleaved-Caspase3, meanwhile decreased protein expression of OPG and Bcl-2 in a dose-dependent manner. LRG inverted PA-induced apoptosis, increased cAMP levels, promoted expression of p-PKA, p-β-catenin and reversed these gene expression via increasing GLP1R expression. Pretreatment of the cells with Exendin 9–39 and H89 partially eradicated the protective effect of LRG on PA-induced apoptosis. Therefore, these findings indicated that LRG attenuates PA-induced apoptosis possibly by GLP1R-mediated PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-L1 cells. Our results point to LRG as a new strategy to attenuate bone loss associated with high fat diet beyond its lipid-lowering actions.