Acetyl-keto-β-boswellic acid induces lipolysis in mature adipocytes

Recently, it was reported that naturally occurring pentacyclic triterpenoids such as ursolic acid have anti-adiposity property. We studied if acetyl-keto-β-boswellic acid (AKBA), an established anti-inflammation and anti-cancer pentacyclic triterpenoid which has similar chemical structure to ursolic acid, may modulate adipocyte phenotype. 3T3-L1 murine adipocytes and human subcutaneous adipocytes were treated with AKBA in different concentrations in vitro. AKBA triggered significant lipolysis in 3T3-L1 adipocytes as shown by reduced neutral lipids in cytosol and increased free fatty acids in culture medium. Increased lipolysis by AKBA was accompanied by up-regulation of lipolytic enzymes, adipocyte triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), and a decreased expression of lipid droplet stability regulator perilipin. In addition, AKBA treatment reduced phenotypic markers of mature adipocyte aP2, adiponectin and glut-4 in mature adipocytes. Further studies revealed that AKBA down-regulated PPAR-γ and C/EBP-α expression in a dose and temporal dependent manner in mature adipocytes. In human adipocytes, AKBA likewise mobilized lipolysis accompanied by down-regulation of PPAR-γ2 expression and loss of phenotypic markers of mature adipocytes.