The antiadipogenic effect of the pentacyclic triterpenoid isoarborinol is mediated by LKB1-AMPK activation

Abstract

Obesity and overweight are two highly prevalent conditions worldwide, which can lead to death or produce chronic and degenerative diseases. The search for alternative therapies to control these morbidities can involve the study of metabolites obtained from plants. Particularly, pentacyclic triterpenes produce an antiadipogenic effect by affecting the expression of master regulators of adipogenesis and their signaling pathways, including LKB1-AMPK pathway. In this work, we evaluated the effect of the pentacyclic triterpene isoarborinol on adipogenesis in 3T3-L1 cells. This molecule inhibits differentiation and decreases lipid accumulation during cell differentiation in a dose-dependent manner, deregulates the expression of C/EBPβ, C/EBPδ, C/EBPα, PPARγ and SREBP-1C, causes an increase in the phosphorylation of LKB1 and AMPK, as well as a down regulation of the lipogenic factors ACC1, FAS and FABP4. These findings show that the antiadipogenic effect of isoarborinol is associated with the activation of LKB1-AMPK, leading to changes in the expression of master regulators of adipogenesis and lipogenic factors.