Monacolin K在HepG2細胞中透過SIRT1/AMPK路徑刺激脂肪分解

Monacolin K最初是從紅麴菌分離的二次代謝產物，之前研究證明，Monacolin K可以經由和3-hydroxy-3-methylglutaryl coenzyme A reductase（HMG-COA）的競爭性抑制，減少低密度脂蛋白（LDL）且增加高密度脂蛋白（HDL）。我們發現Monacolin K在HepG2細胞中會增加NAD-dependent deacetylase sirtuin-1 (SIRT1)的蛋白質濃度和AMP-activated protein kinase（AMPK）的磷酸化，而這個影響被認為與降低脂肪酸合成、高血脂代謝相關。此外，我們還發現，Monacolin K會藉由增加Adipose triglyceride lipase（ATGL）的表現量來增加脂肪分解，並且降低Fatty acid synthase（FAS）和Sterol regulatory element-binding protein 1（SREBP1）的表現量來減少脂肪合成，透過油紅染色法觀察細胞內脂質的堆積也有明顯的減少。而這些現象均可被SIRT1或AMPK的抑製劑Nicotinamide或Compound C所抑制；在先前研究報告指出FoxO1可以透過進入細胞核內調控ATGL的表現，經由我們的結果也發現，Monacolin K 可以減少FoxO1磷酸化而刺激FoxO1轉位至細胞核內促使ATGL的表現量增加。我們的研究結果說明，在HepG2細胞中，Monacolin K會透過SIRT1/AMPK的途徑來減少脂肪堆積現象。

關鍵字

代謝症候群；洛伐他汀；紅麴；脂肪肝

並列摘要

Monacolin K, originally isolated from Monascus spp. as the secondary metabolite, has been previously demonstrated to reduce the synthesis of cholesterol in association with a decrease in low density lipoprotein (LDL) and an increase in high density lipoprotein (HDL) by inhibiting the enzymatic activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In this study, monacolin K was found to increase the protein level of SIRT1 and the phosphorylation level of AMP-activated protein kinase (AMPK) in HepG2 cells, and the effects have been reported to be associated with lower fatty acid synthesis and higher lipid metabolism. Furthermore, we also found that monacolin K inhibited the activity of acteyl CoA carboxylase (ACC) and caused the nuclear translocation of FoxO1 together with their changes in phosphorylation level. To investigate the involvement of monacolin in lipolysis, the protein expression levels of adipocyte triglyceride lipase (ATGL), fatty acid synthase (FAS),sterol regulatory element-binding protein 1 (SREBP1) were determined by western blotting analysis. The results showed that monacolin increased ATGL but decreased FAS and SREBP1 expressions, and some of the effects were counteracted by nicotinamide or compound C, inhibitors of SIRT1 or AMPK. The results were connected with the intracellular lipid level that was decreased by monacolin using the method of oil red staining. In summary, monacolin enhances lipolysis through AMPK/SIRT1 pathway in HepG2 cells.

並列關鍵字

SIRT1 ； AMPK ； ATGL ； Monacolin K

參考文獻

洪綉茹，2005，3T3-L1脂肪細胞培養及分化平台建立及其應用於活性藻類的篩選。國立中央大學生命科學研究所碩士論文。

陳巧玫，2011，研究Ras轉型細胞中lovastatin藥物抑制細胞增生的作用機轉。成功大學藥理學研究所

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Monacolin K在HepG2細胞中透過SIRT1/AMPK路徑刺激脂肪分解

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