College of Food Science and Engineering, Jilin Agricultural University, No. 2888 Xincheng Street, Changchun, Jilin 130118, China.
National Engineering Research Center for Wheat and Corn Deep Processing, No. 2888 Xincheng Street, Changchun, Jilin 130118, China.
Food Funct. 2022 Aug 30;13(17):8892-8906. doi: 10.1039/d2fo01094a.
Cytoplasmic lipid droplets (LDs), which are remarkably dynamic, neutral lipid storage organelles, play fundamental roles in lipid metabolism and energy homeostasis. Both the dynamic remodeling of LDs and LD-mitochondrion interactions in adipocytes are effective mechanisms to ameliorate obesity and related comorbidities. Zeaxanthin (ZEA) is a natural carotenoid and has beneficial effects on anti-obesity. However, the underlying mechanisms of ZEA on LD modulation are still unclear. In the present study, ZEA efficiently inhibited LD accumulation and attenuated adipocyte proliferation by arresting the cell cycle. ZEA drove transcriptional alterations to reprogram a lipid oxidative metabolism phenotype in mature 3T3-L1 adipocytes. ZEA significantly decreased the TAG and FA content and modulated the dynamic alterations of LDs by upregulating the expression of lipases and the LD-mitochondrion contact site protein, perilipin 5 (PLIN5), and downregulating the LD fusion protein, fat-specific protein 27 (FSP27). Mechanistically, ZEA stimulated LD remodeling and ameliorated mitochondrial defects caused by large and unilocular LD accumulation by activating β3-adrenergic receptor (β3-AR) signaling. Furthermore, the knockdown of PLIN5 impaired the LD-mitochondrion interactions, thereby disrupting the role of ZEA in promoting mitochondrial fatty acid oxidation and respiratory chain operation. Collectively, the present study demonstrates that ZEA induces LD structural and metabolic remodeling by activating β3-AR signaling and enhances PLIN5-mediated LD-mitochondrion interactions in hypertrophic white adipocytes, thereby enhancing oxidative capacity, and has the potential as a nutritional intervention for the prevention and treatment of obesity and associated metabolic syndrome.
细胞质脂滴（LDs）是一种显著动态的中性脂质储存细胞器，在脂质代谢和能量平衡中发挥着基本作用。脂肪细胞中 LDs 的动态重塑和 LD-线粒体相互作用是改善肥胖和相关合并症的有效机制。玉米黄质（ZEA）是一种天然类胡萝卜素，对抗肥胖有有益作用。然而，ZEA 对 LD 调节的潜在机制尚不清楚。在本研究中，ZEA 通过阻断细胞周期有效地抑制 LD 积累并减弱脂肪细胞增殖。ZEA 驱动转录变化，在成熟 3T3-L1 脂肪细胞中重新编程脂质氧化代谢表型。ZEA 显著降低 TAG 和 FA 含量，并通过上调脂肪酶和 LD-线粒体接触蛋白 perilipin 5（PLIN5）的表达以及下调 LD 融合蛋白脂肪特异性蛋白 27（FSP27）来调节 LD 的动态变化。在机制上，ZEA 通过激活β3-肾上腺素能受体（β3-AR）信号刺激 LD 重塑，并改善由大而单房 LD 积累引起的线粒体缺陷。此外，PLIN5 的敲低破坏了 LD-线粒体相互作用，从而破坏了 ZEA 在促进线粒体脂肪酸氧化和呼吸链作用中的作用。总之，本研究表明，ZEA 通过激活β3-AR 信号诱导 LD 结构和代谢重塑，并增强肥大白色脂肪细胞中 PLIN5 介导的 LD-线粒体相互作用，从而增强氧化能力，具有作为预防和治疗肥胖和相关代谢综合征的营养干预的潜力。
