YC-1 inhibits lipid droplet accumulation and induces lipolysis in lipid-laden RAW264.7 macrophages

Chih Hui Chin, Tsong Long Hwang, Chao Chien Chang, Chien Liang Liu, Jie Jen Lee, Leo Tsui, Jin-Shan Chen, Tsorng Harn Fong

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 cultured RAW264.7 macrophages with oleic acid (OA) or cobalt chloride (CoCl 2) (a hypoxia mimetic). Morphological observation showed several Nile red-positive lipid droplets in the cytoplasm of OA-treated RAW264.7 macrophages. Pretreatment with 60 μMYC-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 cyclase (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 attenuated CoCl 2-induced lipid droplets accumulation. Our results demonstrated that YC-1 could mediate lipid metabolism in macrophage and reduce foam cell formation, and it could be regarded as a potential drug for the prevention or therapy of atherosclerosis.

Original languageEnglish
JournalJournal of Food and Drug Analysis
Volume19
Issue number4
Publication statusPublished - Dec 2011

Keywords

  • Hypoxia
  • Lipolysis
  • Macrophage
  • Oleic acid
  • YC-1

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

Fingerprint Dive into the research topics of 'YC-1 inhibits lipid droplet accumulation and induces lipolysis in lipid-laden RAW264.7 macrophages'. Together they form a unique fingerprint.

  • Cite this

    Chin, C. H., Hwang, T. L., Chang, C. C., Liu, C. L., Lee, J. J., Tsui, L., Chen, J-S., & Fong, T. H. (2011). YC-1 inhibits lipid droplet accumulation and induces lipolysis in lipid-laden RAW264.7 macrophages. Journal of Food and Drug Analysis, 19(4).