金線連苷透過AMPK和PKA活化下游路徑促使脂肪分解及脂肪酸氧化

Half of the top ten mortality diseases are related with obesity in Taiwan for many years, such as hypertension, diabetes and chronic liver diseases. In addition to the susceptibility of developing cancer, the high blood glucose, blood pressure and blood lipid in obese people are easy to develop fatty liver. Anoectochilus formosanus has anti-oxidation, anti-inflammation, and antihyperliposis activities. Previous study showed that one of the major compounds in Anoectochilus formosanus, kinsenoside, can induce lipolysis. We aim to illustrate the catabolic effects of kinsenoside on lipolysis and fatty acid oxidation in C3H10T1/2 cells transformed by adipocyte inducing medium and in vivo. Our findings demonstrated that kinsenoside increases lipolysis by ATGL and HSL, which are upregulated by AMPK and PKA activation, respectively. We observe that kinsenoside increases hydrolysis of triglyceride to glycerol and fatty acids that are further transported into mitochondria for β-fatty acid oxidation. Results of this study also demonstrate that kinsenoside increases the protein levels of SIRT1, PGC1α, p-PPARα, p-CREB and CPT1 by AMPK activation both in vitro and in vivo. SIRT1 deacetylates PGC1α to increase PGC1α activity that in turn interacts with PPARα to increase the transcription of β-oxidation related protein, CPT1. In addition, PGC1α is upregulated by AMPK-mediated-CREB activation. Therefore, AMPK activation is also responsible for the increased β-oxidation induced by kinsenoside. In summary, we demonstrate that the effects of kinsenoside in lipolysis and fatty acid oxidation and its underlying mechanisms are through AMPK or PKA-dependent pathways.