Unexpected omega-3 activities in intracellular lipolysis and macrophage foaming revealed by fluorescence lifetime imaging

• 成果类型: Article
• 署名作者: Tang, Hesen; Liu, Zhengjie; Han, Guangmei; Geng, Junlong; Liu, Bianhua; Zhang, Ruilong; Zhang, Zhongping
• 署名单位: Anhui University; Chinese Academy of Sciences; Hefei Institutes of Physical Science, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14444
• DOI: 10.1073/pnas.2321255121
• 发表日期: 2024-04-09
• 关键词: lipid droplets; eicosapentaenoic acid; triglyceride; autophagy; promotes; biology; probe

摘要

Omega - 3 polyunsaturated fatty acids (PUFA) found primarily in fish oil have been a popular supplement for cardiovascular health because they can substantially reduce circulating triglyceride levels in the bloodstream to prevent atherosclerosis. Beyond this established extracellular activity, here, we report a mode of action of PUFA, regulating intracellular triglyceride metabolism and lipid droplet (LD) dynamics. Real - time imaging of the subtle and highly dynamic changes of intracellular lipid metabolism was enabled by a fluorescence lifetime probe that addressed the limitations of intensity - based fluorescence quantifications. Surprisingly, we found that among omega - 3 PUFA, only docosahexaenoic acid (DHA) promoted the lipolysis in LDs and reduced the overall fat content by approximately 50%, and consequently helped suppress macrophage differentiation into foam cells, one of the early steps responsible for atherosclerosis. Eicosapentaenoic acid, another omega - 3 FA in fish oil, however, counteracted the beneficial effects of DHA on lipolysis promotion and cell foaming prevention. These in vitro findings warrant future validation in vivo.