Thiacremonone, a sulfur compound isolated from garlic, attenuates lipid accumulation partially mediated via AMPK activation in 3T3-L1 adipocytes
Thiacremonone, a sulfur compound isolated from garlic, attenuates lipid accumulation partially mediated via AMPK activation in 3T3-L1 adipocytes
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DOI：
10.1016/j.jnutbio.2011.10.008
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发表时间：
2012-12-01
影响因子：
5.6
通讯作者：
Yoon, Do Young
中科院分区：
文献类型：
--
作者：
Kim, Eun Jin;Lee, Dong Hun;Yoon, Do Young
大蒜提取物具有抗癌和抗炎的作用。然而，大蒜衍生化合物的抗脂肪作用仍不清楚。在这项研究中，我们用3T3-L1细胞研究了从大蒜中分离出的硫化物--硫杂黄酮酮对脂肪细胞分化的影响。我们发现，噻酮通过下调成脂相关转录因子和成脂标记物的表达，显著抑制3T3-L1分化。抑制作用主要发生在3T3-L1细胞分化的早期。对3T3-L1细胞无细胞毒作用，用其诱导3T3-L1细胞分化可引起AMPK激活，导致脂肪酸合成和利用所必需的乙酰辅酶A羧基酶-1(ACC-1)表达减弱。此外，噻吩酮还可提高肉碱棕榈酰转移酶(CPT-1)的mRNA水平。用AMPK抑制剂化合物C处理后，可部分消除硫去氧尿酮对脂解相关基因表达的调节作用。综上所述，这些结果表明，硫去氧尿酮诱导的AMPK激活、ACC-1表达的抑制和CPT-1表达的恢复导致了细胞内脂滴水平的抑制，提示硫去氢酮可能通过激活AMPK而导致细胞内脂质合成减少和脂肪酸氧化增加。硫酮可能是治疗肥胖症的一种有前途的化合物。(C)2012 Elsevier Inc.保留所有权利。
Garlic extracts exert anti-cancer and anti-inflammatory effects. However, the anti-adipogenic effect of garlic-derived compounds remains unclear. In this study, we examined the effect of thiacremonone, a sulfur compound isolated from garlic, on adipocyte differentiation using 3T3-L1 cells. We found that thiacremonone significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation in 3T3-L1 cells. There was no cytotoxic effect of thiacremonone in 3T3-L1 cells and treatment of differentiating 3T3-L1 cells with thiacremonone resulted in AMPK activation, which led to an attenuated expression of acetyl CoA carboxylase-1 (ACC-1), an essential enzyme for the synthesis and usage of fatty acids. Moreover, thiacremonone enhanced the mRNA level of carnitine palmitoyltransferase (CPT-1). The modulating effect of thiacremonone on expressions of genes involved in lipolysis was partially abrogated by treatment with compound C, an AMPK inhibitor. Taken together, these results indicated that thiacremonone-induced AMPK activation, inhibition of ACC-1 expression and concomitant recovery of CPT-1 expression resulted in the suppression of intracellular lipid droplet levels, suggesting that thiacremonone may induce reduction of lipid synthesis and increases in fatty acid oxidation partially mediated via AMPK activation. Thiacremonone may be a promising compound for the treatment of obesity. (C) 2012 Elsevier Inc. All rights reserved.