Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828, Republic of Singapore.
Biochem Biophys Res Commun. 2013 Feb 8;431(2):192-6. doi: 10.1016/j.bbrc.2012.12.136. Epub 2013 Jan 9.
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.
最近有报道称，熊果酸等天然五环三萜具有抗肥胖特性。我们研究了乙酰基-酮-β-乳香酸（AKBA）是否可以调节脂肪细胞表型，AKBA 是一种已被证实的具有类似化学结构的五环三萜抗炎和抗癌药物。体外将 AKBA 以不同浓度作用于 3T3-L1 小鼠脂肪细胞和人皮下脂肪细胞。AKBA 可显著触发 3T3-L1 脂肪细胞的脂肪分解，表现为细胞质中中性脂质减少和培养基中游离脂肪酸增加。AKBA 引起的脂肪分解增加伴随着脂肪分解酶、脂肪甘油三酯脂肪酶（ATGL）和激素敏感脂肪酶（HSL）的上调，以及脂质滴稳定性调节剂 perilipin 的表达下调。此外，AKBA 处理可降低成熟脂肪细胞 aP2、脂联素和葡萄糖转运蛋白 4（glut-4）等成熟脂肪细胞的表型标志物。进一步的研究表明，AKBA 以剂量和时间依赖的方式下调成熟脂肪细胞中过氧化物酶体增殖物激活受体 γ（PPAR-γ）和 C/EBP-α 的表达。在人脂肪细胞中，AKBA 同样可动员脂肪分解，同时下调 PPAR-γ2 的表达，并丧失成熟脂肪细胞的表型标志物。
