Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, PR China.
Mol Nutr Food Res. 2010 Nov;54(11):1609-17. doi: 10.1002/mnfr.200900564.
Ursolic acid (UA) is a pentacyclic triterpenic acid with many biological functions naturally existing in many kinds of food. To investigate whether UA can accelerate lipolysis, primary-cultured rat adipocytes were treated with UA, and glycerol release in the culture medium was measured. UA stimulated lipolysis significantly. Furthermore, the lipolytic effect of UA was inhibited by the protein kinase A (PKA) specific inhibitor H89, suggesting that UA exerted its lipolytic function through the cAMP-dependent PKA pathway. Downstream targets of the PKA pathway, hormone-sensitive lipase (HSL) and perilipin A were checked, UA enhanced lipolysis by promoting the translocation of HSL from the cytosol to the lipid droplets and inhibiting the expression of perilipin A. Additionally, adipose triglyceride lipase (ATGL), a novel rate-limiting lipase in the lipolytic catabolism, was upregulated by UA. UA-induced expression of ATGL could not be blocked by H89, suggesting that ATGL upregulation is not regulated by the PKA pathway. These findings suggest that UA significantly stimulates lipolysis by translocating HSL, decreasing perilipin A expression by the PKA pathway, and up-regulating ATGL in primary cultured adipocytes. Thus, UA is a promising candidate for the treatment of obesity.
熊果酸（UA）是一种五环三萜酸，具有许多生物学功能，天然存在于许多种食物中。为了研究 UA 是否能加速脂肪分解，用 UA 处理原代培养的大鼠脂肪细胞，并测量培养基中甘油的释放量。UA 显著刺激脂肪分解。此外，UA 的脂肪分解作用被蛋白激酶 A（PKA）特异性抑制剂 H89 抑制，表明 UA 通过 cAMP 依赖性 PKA 途径发挥其脂肪分解功能。检查了 PKA 途径的下游靶标激素敏感性脂肪酶（HSL）和脂滴包被蛋白 A（ perilipin A），UA 通过促进 HSL 从细胞质向脂滴的易位并抑制 perilipin A 的表达来增强脂肪分解。此外，脂肪甘油三酯脂肪酶（ATGL），脂肪分解代谢中的一种新型限速脂肪酶，被 UA 上调。UA 诱导的 ATGL 表达不能被 H89 阻断，表明 ATGL 的上调不受 PKA 途径的调节。这些发现表明，UA 通过易位 HSL 显著刺激脂肪分解，通过 PKA 途径降低 perilipin A 的表达，并在原代培养的脂肪细胞中上调 ATGL。因此，UA 是治疗肥胖症的有前途的候选药物。
