Wang Guihua, Sun Xiaonan, Chen Xin, Zhang Lejie, Fan Shaoqiang, Mu Yu, Zheng Dan, Huang Xueshi, Xu Jialin, Li Liya
Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China; School of Chemical Engineering, Yunnan Open University, Kunming 650500, China.
The Fourth People's Hospital of Shenyang, Shenyang 110031, China.
Biochem Pharmacol. 2025 Jul 11;241:117136. doi: 10.1016/j.bcp.2025.117136.
Syzygium cumini is an edible berry with anti-diabetic and anti-obesity activities. However, to date, the major bioactive components contributing to S. cumini's effects against metabolic disorders still remain unclear. Phenolipids with chroman/chromone skeleton and long alkyl side chain are characteristic constituents of S. cumini. In the current study, we explored anti-obesity effects and underlying mechanism of jambone E (JE), a representative phenolipid of S. cumini, with high-fat diet (HFD)-fed mice and cellular models. Our data demonstrated that JE supplementation (at dosages of 75 and 150 mg/kg) for 10 weeks significantly attenuated HFD-induced body weight gain, adipocyte hypertrophy, and hyperlipidemia in mice, promoted insulin receptor β/protein kinase B-mediated insulin signaling transduction in liver, adipose tissue, and skeletal muscles, inhibited proinflammatory factors release in adipose tissue with downregulated nuclear factor kappa-B/NOD-like receptor thermal protein domain associated protein 3 signaling pathway. The 16S rRNA gene sequencing, gas chromatography-mass spectrometry, and ultra-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry analysis revealed that JE intervention increased relative abundance of Bifidobacterium genus in fecal samples, promoted gut-derived acetic acid production, and reshaped fecal bile acid profiles in HFD-fed mice. Further molecular mechanism study suggested that JE supplementation to HFD-fed mice augmented the expression of bile acid metabolism related genes including Fxr, Cyp8b1, Cyp7b1, and Cyp27a1, whilst downregulated lipid metabolism related gene Acc1 expression in the liver. Moreover, cellular study revealed that JE treatment could reduce total cholesterol and triglyceride synthesis and increase bile acid secretion in HepG2 cells. Our work suggested the association of anti-obesity effects of JE and microbiota-bile acid-farnesoid X receptor axis, and highlighted the potential utilization of JE and its analogues in treating obesity and related comorbidities.
乌墨是一种具有抗糖尿病和抗肥胖活性的可食用浆果。然而，迄今为止，乌墨对代谢紊乱作用的主要生物活性成分仍不清楚。具有色满/色酮骨架和长烷基侧链的酚脂是乌墨的特征成分。在本研究中，我们利用高脂饮食（HFD）喂养的小鼠和细胞模型，探讨了乌墨代表性酚脂——乌墨酮E（JE）的抗肥胖作用及其潜在机制。我们的数据表明，JE以75和150 mg/kg的剂量补充10周，可显著减轻HFD诱导的小鼠体重增加、脂肪细胞肥大和高脂血症，促进肝脏、脂肪组织和骨骼肌中胰岛素受体β/蛋白激酶B介导的胰岛素信号转导，抑制脂肪组织中促炎因子的释放，下调核因子κB/核苷酸结合寡聚化结构域样受体热蛋白结构域相关蛋白3信号通路。16S rRNA基因测序、气相色谱-质谱联用和超高效液相色谱-四极杆-飞行时间/质谱分析表明，JE干预增加了HFD喂养小鼠粪便样本中双歧杆菌属的相对丰度，促进了肠道衍生乙酸的产生，并重塑了粪便胆汁酸谱。进一步的分子机制研究表明，向HFD喂养的小鼠补充JE可增加肝脏中包括法尼酯X受体（Fxr）、细胞色素P450 8B1（Cyp8b1）、细胞色素P450 7B1（Cyp7b1）和细胞色素P450 27A1（Cyp27a1）在内的胆汁酸代谢相关基因的表达，同时下调肝脏中脂质代谢相关基因乙酰辅酶A羧化酶1（Acc1）的表达。此外，细胞研究表明，JE处理可降低HepG2细胞中总胆固醇和甘油三酯的合成，并增加胆汁酸分泌。我们的研究表明了JE的抗肥胖作用与微生物群-胆汁酸-法尼酯X受体轴之间的关联，并突出了JE及其类似物在治疗肥胖症和相关合并症方面的潜在应用价值。
