Division of Geriatric Medicine, Tongji Hospital, Tongji University, Shanghai 200065, China.
Phytomedicine. 2012 Dec 15;20(1):3-8. doi: 10.1016/j.phymed.2012.09.003. Epub 2012 Oct 17.
Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes.
Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation.
Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05).
This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity.
姜黄素是从香料姜黄(Curcuma longa)中提取的一种活性成分,已被证明具有抗高血糖、抗炎和降胆固醇作用,可用于肥胖和糖尿病。这些作用与循环游离脂肪酸(FFA)水平降低有关,但机制尚未阐明。FFA 和甘油从脂肪组织到血液的通量主要取决于脂肪细胞中三酰甘油的脂解。脂肪细胞的脂解作用受儿茶酚胺激素的生理性刺激。肿瘤坏死因子-α(TNFα)刺激肥胖和 2 型糖尿病中的慢性脂解作用。在这项研究中,我们研究了姜黄素在抑制 3T3-L1 脂肪细胞受到各种刺激时的脂解作用中的作用。
使用比色法(GPO-Trinder)测定 TNFα 或异丙肾上腺素刺激的 3T3-L1 脂肪细胞中无或有姜黄素时的甘油释放量。使用 Western blot 分析检测 TNFα 诱导的 MAPK 磷酸化和脂联素表达。制备 Fatcake 和胞质部分以检查异丙肾上腺素刺激的激素敏感脂肪酶易位。
姜黄素处理可通过抑制细胞外信号相关激酶 1/2(ERK1/2)的磷酸化并逆转 TNFα 刺激的脂肪细胞中脂联素蛋白的下调来减轻 TNFα 介导的脂解作用(p<0.05)。姜黄素还限制了肾上腺素能刺激异丙肾上腺素的急性脂解反应(10-20 μM,p<0.05),这与减少的脂联素磷酸化(29%,p<0.05)和激素敏感脂肪酶易位(20%,p<0.05)一致。
这项研究提供的证据表明,姜黄素作用于脂肪细胞以抑制 TNFα 和儿茶酚胺的脂解反应。抗脂解作用可能是姜黄素降低血浆 FFA 水平和改善胰岛素敏感性的细胞基础。