YC-1 Inhibits Lipid Droplet Accumulation and Induces Lipolysis in Lipid-Laden RAW264.7 Macrophages

藥物YC－l對於RAW264.7巨噬細胞內脂肪滴堆積現象具有抑制作用並且可以誘發脂質分解

秦志輝(Chih-Hui Chin) ； 黃聰龍(Tsong-Long Hwang) ； 張釗監(Chao-Chien Chang) ； 劉建良(Chien-Liang Liu) ； 李居仁(Jie-Jen Lee) ； 崔立有(Leo Tsui) ； 陳金山(Jin-Shan Chen) ； 馮琮涵(Tsorng-Harn Fong)

《藥物食品分析》 19卷4期 (2011/12) Pp. 437-444

並列摘要

Macrophage foam cells play a central role in the initiation and progression of atherosclerosis. The present study investigates the effect of YC-1, a synthetic benzylindazole compound, on lipid metabolism in macrophage-derived foam cells. Foam cell formation was induced by incubating culturcd RAW264,7 macrophages with oleic acid (OA) or cobalt chloride (CoCI2) (a hypoxia mimetic), Morphological observation showed several Nile red-positive lipid droplets in the cytoplasm of OA-treated RAW264.7 macrophages, Pretreatment with 60 μM YC-1 could inhibit lipid accumulation. Co-incubation with OA and YC-1 also attenuated lipid accumulation due to the decrease in surface area of lipid droplets. Post-treatment with YC-1 induced lipolysis and free fatty acid release in lipid-laden macrophages in both dose- and time-dependent manners. In addition, ODQ, a soluble guanynyl cyclasc (sGC) inhibitor, could not reverse the inhibitory effect of YC-1 on lipid accumulation, or block the lipolytic effect of YC-1 in lipid-laden macrophages. Neither another nitric oxide-independent sGC activator (BAY 41-2272) nor dibutyryl cGMP (db-cGMP) could mimic the effects of YC-1. Both intracellular sGC activity and the cGMP level remained unchanged following YC-1 incubation. These results suggested that the mechanism of YC-1-mediated lipid metabolism was via an sGC/cGMP-independent signal transduction pathway in RAW264.7 macrophages. In addition, YC-1 significantly attenuatced CoCl2-induced lipid droplets accumulation. Our results demonstrated that YC-1 could mediate lipid metabolism in macro phage and reduce foam cell formation, and it could be regarded as a potential drug for the prevention or therapy of atherosclerosis.

並列關鍵字

hypoxia ； lipolysis ； macrophage ； oleic acid ； YC-1