College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, China.
National Engineering Laboratory for Wheat and Corn Deep Processing, Changchun, Jilin 130118, China.
Food Funct. 2021 Dec 13;12(24):12734-12750. doi: 10.1039/d1fo02863d.
The stimulation of fat thermogenesis and modulation of the gut microbiota are promising therapeutic strategies against obesity. Zeaxanthin (ZEA), a carotenoid plant pigment, has been shown to prevent various diseases; however, the therapeutic mechanism for obesity remains unclear. Herein, whether ZEA improves obesity by activating the β3-adrenergic receptor (β3-AR) to stimulate white adipose tissue (WAT) thermogenesis and modulating the gut microbiota was investigated. C57BL6/N mice were fed a high-fat diet (HFD) supplemented with ZEA for 22 weeks. ZEA treatment reduced body weight, fat weight, adipocyte hypertrophy, liver weight, and lipid deposition, and improved dyslipidaemia, serum GPT, GOT, leptin, and irisin levels, glucose intolerance, and insulin resistance in HFD-fed mice. Mechanistically, ZEA treatment induced the expression of β3-AR and thermogenic factors, such as PRDM16, PGC-1α, and UCP1, in inguinal WAT (iWAT) and brown adipose tissue. ZEA treatment stimulated iWAT thermogenesis through the synergistic cooperation of key organelles, which manifested as an increased expression of lipid droplet degradation factors (ATGL, CGI-58 and pHSL), mitochondrial biogenesis factors (, , , and ), peroxisomal biogenesis factors (, and ), and β-oxidation factors (, , and ). The thermogenic effect of ZEA was abolished by β3-AR antagonist (SR59230A) treatment. Additionally, dietary supplementation with ZEA reversed gut microbiota dysbiosis by regulating the abundance of Firmicutes, Clostridia, Proteobacteria, and , which were associated with the thermogenesis- and obesity-associated indices by Spearman's correlation analysis. Functional analysis of the gut microbiota indicated that ZEA treatment significantly enriched the lipid metabolism pathways. These results demonstrate that ZEA is a promising multi-target functional food for the treatment of obesity by activating β3-AR to stimulate iWAT thermogenesis, and modulating the gut microbiota.
脂肪产热的刺激和肠道微生物群的调节是治疗肥胖症的有前途的治疗策略。玉米黄质（ZEA）是一种类胡萝卜素植物色素，已被证明可预防各种疾病；然而，肥胖症的治疗机制尚不清楚。在此，通过激活β3-肾上腺素能受体（β3-AR）刺激白色脂肪组织（WAT）产热并调节肠道微生物群来研究 ZEA 是否改善肥胖症。C57BL6/N 小鼠用高脂肪饮食（HFD）补充 ZEA 喂养 22 周。ZEA 处理可降低体重、脂肪重量、脂肪细胞肥大、肝重和脂质沉积，并改善 HFD 喂养小鼠的血脂异常、血清 GPT、GOT、瘦素和鸢尾素水平、葡萄糖耐量和胰岛素抵抗。在机制上，ZEA 处理诱导腹股沟 WAT（iWAT）和棕色脂肪组织中β3-AR 和产热因子（如 PRDM16、PGC-1α 和 UCP1）的表达。ZEA 处理通过关键细胞器的协同合作刺激 iWAT 产热，表现为脂滴降解因子（ATGL、CGI-58 和 pHSL）、线粒体生物发生因子（、、、和）、过氧化物酶体生物发生因子（和）和β-氧化因子（和）的表达增加。β3-AR 拮抗剂（SR59230A）处理可消除 ZEA 的产热作用。此外，膳食补充 ZEA 通过调节厚壁菌门、梭菌、变形菌门和的丰度来逆转肠道微生物群失调，通过 Spearman 相关分析与产热和肥胖相关指标相关。肠道微生物群的功能分析表明，ZEA 处理显著丰富了脂质代谢途径。这些结果表明，ZEA 通过激活β3-AR 刺激 iWAT 产热和调节肠道微生物群，是一种有前途的用于治疗肥胖症的多靶功能食品。
