Key Laboratory of Horticulture Science for Southern Mountainous Regions of Ministry of Education, College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400715, China.
Key Laboratory of Horticulture Science for Southern Mountainous Regions of Ministry of Education, College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400715, China; The Southwest Institute of Fruits Nutrition, Banan District, Chongqing 400054, China.
J Nutr Biochem. 2022 Mar;101:108943. doi: 10.1016/j.jnutbio.2022.108943. Epub 2022 Jan 10.
Obesity and associated comorbidities are closely linked to gut microbiota dysbiosis, energy balance, and chronic inflammation. Tangeretin, a key citrus polymethoxylated flavone (PMF), is abundant in citrus fruits and has preventative and therapeutic effects for numerous diseases. The current study investigated the effects and possible mechanisms of tangeretin supplementation in preventing obesity in high-fat diet (HFD)-fed mice. Treatment of HFD-fed mice with tangeretin potently ameliorated HFD-induced body weight, liver steatosis, glucose intolerance, and insulin resistance. Tangeretin mitigated systemic chronic inflammation by reducing metabolic endotoxemia and inflammation-related gene expression in HFD-fed mice. An increased number of small brown adipocytes possessing multilocular and cytoplasmic lipid droplets and upregulation of thermogenic gene expression were observed after tangeretin treatment. 16S rRNA amplicon sequencing indicated that tangeretin markedly altered the gut microbiota composition (richness and diversity) and reversed 16 operational taxonomic units (OTUs) back to levels seen in mice consuming a normal chow diet (NCD). Notably, tangeretin decreased the ratio of Firmicutes-to-Bacteroidetes and greatly enriched Bacteroides and Lactobacillus. Overall, our results suggest that long-term supplementation with citrus tangeretin ameliorates the phenotype of obesity by improving adipose thermogenesis and reducing systemic inflammation and gut microbiota dysbiosis, which provides a good basis for studying the mechanism of tangeretin's beneficial effects.
肥胖及其相关合并症与肠道微生物失调、能量平衡和慢性炎症密切相关。桔皮素是一种重要的柑橘多甲氧基黄酮（PMF），在柑橘类水果中含量丰富，对许多疾病具有预防和治疗作用。本研究探讨了桔皮素补充剂预防高脂肪饮食（HFD）喂养小鼠肥胖的作用及其可能机制。桔皮素治疗 HFD 喂养的小鼠可有效改善 HFD 诱导的体重、肝脂肪变性、葡萄糖不耐受和胰岛素抵抗。桔皮素通过降低代谢内毒素血症和炎症相关基因在 HFD 喂养小鼠中的表达，减轻了全身慢性炎症。在桔皮素处理后，观察到具有多泡和细胞质脂质滴的小棕色脂肪细胞数量增加，并且产热基因表达上调。16S rRNA 扩增子测序表明，桔皮素显著改变了肠道微生物群落组成（丰富度和多样性），并将 16 个操作分类单元（OTUs）中的 16 个逆转回正常饲料饮食（NCD）喂养小鼠的水平。值得注意的是，桔皮素降低了厚壁菌门与拟杆菌门的比例，并极大地丰富了拟杆菌属和乳杆菌属。总的来说，我们的研究结果表明，长期补充柑橘桔皮素通过改善脂肪组织的产热作用，减少全身炎症和肠道微生物失调，改善肥胖表型，为研究桔皮素有益作用的机制提供了良好的基础。
