Institute of Physical Science and Information Technology, School of Chemistry and Chemical Engineering, Information Materials and Intelligent Sensing Laboratory of Anhui Province, Key Laboratory of Structure and Functional Regulation of Hybrid Materials of Ministry of Education, Anhui University, Hefei, Anhui 230601, China.
Institute of Solid State Physics, Academy of Chinese Sciences, Hefei, Anhui 230031, China.
Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2321255121. doi: 10.1073/pnas.2321255121. Epub 2024 Apr 2.
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.
ω-3 多不饱和脂肪酸（PUFA）主要存在于鱼油中，因其能显著降低血液中循环甘油三酯水平，从而预防动脉粥样硬化，所以一直是一种颇受欢迎的心血管保健品。除了这种已确立的细胞外活性之外，在这里，我们还报告了 PUFA 的一种作用模式，即调节细胞内甘油三酯代谢和脂滴（LD）动力学。通过一种荧光寿命探针实现了对细胞内脂质代谢的微妙和高度动态变化的实时成像，该探针解决了基于强度的荧光定量的局限性。令人惊讶的是，我们发现，在 ω-3 PUFA 中，只有二十二碳六烯酸（DHA）能促进 LD 中的脂解作用，并使总脂肪含量降低约 50%，从而有助于抑制巨噬细胞分化为泡沫细胞，这是动脉粥样硬化早期的一个重要步骤。然而，另一种存在于鱼油中的 ω-3 FA——二十碳五烯酸（EPA）却抵消了 DHA 促进脂解和预防细胞泡沫化的有益作用。这些体外发现值得未来在体内进行验证。
