Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
Arch Pharm Res. 2013 Dec;36(12):1541-51. doi: 10.1007/s12272-013-0150-2. Epub 2013 May 9.
Monacolin K is the secondary metabolite isolated from Monascus spp. It is the natural form of lovastatin, which is clinically used to reduce the synthesis of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. In the present study, monacolin K increased protein expression of SIRT1 and phosphorylation level of AMP-activated protein kinase (AMPK) in HepG2 cells. Through activation of SIRT1/AMPK pathway, monacolin K increased phosphorylation of acetyl CoA carboxylase and caused nuclear translocation of forkhead box O1. The western blotting results showed that monacolin K increased expression of adipose triglyceride lipase but decreased abundances of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP1). Monacolin K also decreased the intracellular accumulation of lipids as demonstrated by Oil Red O staining. In addition, the immunostaining showed that monacolin K prevented the nuclear translocation of SREBP1, indicating the association with down-regulation of FAS. All the demonstrated effects of monacolin K were counteracted by nicotinamide or compound C, the inhibitors of SIRT1 or AMPK. In summary, monacolin K reduces the lipid content through SIRT1/AMPK pathway in HepG2 cells, which promotes catabolism and inhibits anabolism of lipid.
莫纳可林 K 是从红曲菌属中分离得到的次级代谢产物。它是洛伐他汀的天然形式，临床上用于通过抑制 3-羟基-3-甲基戊二酰辅酶 A 还原酶来减少胆固醇的合成。在本研究中，莫纳可林 K 增加了 HepG2 细胞中 SIRT1 的蛋白表达和 AMP 激活蛋白激酶（AMPK）的磷酸化水平。通过激活 SIRT1/AMPK 通路，莫纳可林 K 增加了乙酰辅酶 A 羧化酶的磷酸化，并导致叉头框 O1 的核转位。Western blot 结果表明，莫纳可林 K 增加了脂肪甘油三酯脂肪酶的表达，同时降低了脂肪酸合成酶（FAS）和固醇调节元件结合蛋白 1（SREBP1）的丰度。莫纳可林 K 还通过油红 O 染色显示减少了细胞内脂质的积累。此外，免疫染色表明，莫纳可林 K 阻止了 SREBP1 的核转位，表明与 FAS 的下调有关。所有这些莫纳可林 K 的作用都被烟酰胺或化合物 C 所拮抗，SIRT1 或 AMPK 的抑制剂。综上所述，莫纳可林 K 通过 SIRT1/AMPK 通路降低 HepG2 细胞中的脂质含量，促进脂质的分解代谢和抑制合成代谢。
