Obesity is associated with numerous metabolic disorders, and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity. However, the effect of 3-(3′,4′-dihydroxyphenyl)propanoic acid (DHPA) and 3′,4′-dihydroxyphenylacetic acid (DHAA), two main metabolites of dietary polyphenols, on obesity remains poorly understood. In this study, DHPA and DHAA were found to alleviate obesity, as well as regulate insulin resistance, lipid metabolism, and oxidative stress response in high-fat diet (HFD) mice. Surprisingly, the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome, but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion, tyrosine metabolism, pentose phosphate and tricarboxylic acid (TCA) cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Correlation analysis revealed that the differential metabolites are strongly associated with body weight, blood glucose, insulin level, and superoxide dismutase (SOD) enzyme activity. Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose, lipid and tyrosine metabolism pathways.

肥胖与许多代谢紊乱有关，膳食多酚已被证实对肥胖的代谢具有有益作用。然而，膳食多酚的两种主要代谢物 3-(3',4'-二羟基苯基)丙酸 (DHPA) 和 3',4'-二羟基苯基乙酸 (DHAA) 对肥胖的影响仍知之甚少。在这项研究中，发现 DHPA 和 DHAA 可以缓解高脂饮食 (HFD) 小鼠的肥胖，并调节胰岛素抵抗、脂质代谢和氧化应激反应。令人惊讶的是，16S rRNA测序和UHPLC-Q-TOF/MS表明DHPA和DHAA仅轻微扰乱肠道微生物组，但主要通过调节戊糖和葡萄糖醛酸相互转化、酪氨酸代谢、基于京都基因和基因组百科全书 (KEGG) 数据库的代谢途径分析表明戊糖磷酸和三羧酸 (TCA) 循环。相关分析显示，差异代谢物与体重、血糖、胰岛素水平和超氧化物歧化酶（SOD）酶活性密切相关。我们的结果表明，DHPA 和 DHAA 通过调节葡萄糖、脂质和酪氨酸代谢途径中的重要代谢物发挥其抗肥胖作用。