目的 探讨蒲公英多糖（dandelion polysaccharide，DP）对高脂饮食诱导的肥胖小鼠肝脏脂质代谢紊乱以及肠道菌群结构的影响。方法 将40只SPF级雄性C57BL/6J小鼠随机分为对照组、模型组、奥利司他（10 mg/kg）组和DP低、高剂量（200、400 mg/kg）组，每组8只。小鼠给予高脂饲料喂养构建肥胖模型，造模同时ig给药8周。给药结束后，小鼠摘眼球采血后处死，取血清，测定总胆固醇（total cholesterol，TC）、三酰甘油（triglyceride，TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）水平；采用苏木素-伊红（hematoxylin-eosin，HE）染色和油红O染色观察小鼠肝脏和附睾脂肪的病理学变化；采用qRT-PCR检测肝脏组织脂代谢相关基因[肉碱棕榈酰转移酶1（carnitine palmitoyltransferase 1，CPT-1）、细胞色素P450家族7亚家族A成员1（cytochrome P450 family 7 subfamily A member 1，CYP7A1）、过氧化物酶体增殖物激活受体α（peroxisome proliferator-activated receptor α，PPARα）、脂肪酸合酶（fatty acid synthase，FAS）、过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ，PPARγ）、硬脂酰辅酶A去饱和酶1（stearoyl-CoA desaturase 1，SCD-1）、激素敏感性脂肪酶（hormone-sensitive lipase，HSL）、脂肪甘油三酯脂肪酶（adipose triglyceride lipase，ATGL）]的表达；收集各组小鼠粪便进行微生物组学测序。结果 与对照组比较，模型组小鼠体质量、附睾脂肪指数及血清中TC、TG、LDL-C水平显著升高（P＜0.01、0.001），HDL-C水平显著降低（P＜0.01），肝脏细胞结构破坏，细胞间隙不清晰，肝索排列明显紊乱，空泡面积和脂滴数量显著增加（P＜0.001），附睾脂肪细胞体积明显增大，细胞形态大小不一；脂肪生成相关基因FAS、PPARγ、SCD-1 mRNA的表达量显著升高（P＜0.01），脂肪分解相关基因HSL和ATGL mRNA的表达量显著降低（P＜0.01）。与模型组比较，DP高、低剂量组和奥利司他组均不同程度地降低肥胖小鼠体质量、附睾脂肪指数，改善肝脏组织和附睾脂肪的组织病理形态，且DP高剂量组脂肪合成相关基因FAS、PPARγ、SCD-1的表达量显著降低（P＜0.01），脂肪分解及氧化相关基因HSL、ATGL、CTP-1、CYP7A1、PPARα mRNA的表达量显著升高（P＜0.01）。同时，DP能够在一定程度上调节肥胖小鼠肠道微生物的物种组成，显著增加Blautia、s_unclassified_g_Lachnospiraceae_NK4A136_group、Lachnospiraceae_bacterium_28-4及Helicoacter rodentium的相对丰度，降低丹毒杆菌属、Ruminococcus_torques_group的相对丰度，并且其优势菌种与脂肪氧化分解基因HSL、ATGL、CTP-1、CYP7A1、PPARα呈正相关，与脂肪合成基因FAS、PPARγ、SCD-1呈负相关。结论 DP能显著降低高脂饮食诱导的肥胖小鼠的体质量，其机制可能与调节有益菌来促进脂肪氧化分解、抑制脂肪合成有关。

Objective To investigate the effect of dandelion polysaccharide (DP) on lipid metabolism disorder in liver and gut microbiota structure in high-fat diet-induced obese mice. Methods A total of 40 SPF male C57BL/6J mice were randomly divided into control group, model group, orlistat (10 mg/kg) group, DP low-, high-dose (200, 400 mg/kg) groups, with eight mice in each group. Mice were fed with high-fat diet to establish an obesity model, and the model was simultaneously administered with ig for eight weeks. After the end of administration, mice were euthanized by removing their eyeballs and collecting blood. Serum was collected to measure the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); Hematoxylin-eosin (HE) staining and Oil red O staining were used to observe the pathological changes of liver and epididymal fat in mice; qRT-PCR was used to detect the expressions of lipid metabolism related genes [carnitine palmitoyltransferase 1 (CPT-1), cytochrome P450 family 7 subfamily A member 1 (CYP7A1), peroxisome proliferator-activated receptor α (PPARα), fatty acid synthase (FAS), peroxisome proliferator-activated receptor γ (PPARγ), stearoyl-CoA desaturase 1 (SCD-1), hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL)] in liver tissue; Feces were collected from each group of mice for microbiome sequencing. Results Compared with control group, the body weight, epididymal fat index, and levels of TC, TG, LDL-C in serum of mice in model group were significantly increased (P < 0.01, 0.001), HDL-C level were significantly decreased (P < 0.01). The structure of liver cells was damaged, the intercellular space was unclear, the arrangement of hepatic cords was significantly disordered, the area of vacuoles and the number of lipid droplets were significantly increased (P < 0.001), and the volume of epididymal fat cells was significantly increased with varying cell shapes and sizes. The expression levels of fat generation related genes FAS, PPARγ and SCD-1 mRNA were significantly increased (P < 0.01), while the expression levels of fat breakdown related genes HSL and ATGL mRNA were significantly decreased (P < 0.01). Compared with model group, DP low-, high-dose groups and orlistat group all reduced the body weight and epididymal fat index of obese mice to varying degrees, and improved the histopathological morphology of liver tissue and epididymal fat. The expression levels of fat synthesis related genes FAS, PPARγ and SCD-1 were significantly reduced in DP high dose group (P < 0.01), while the expression levels of fat breakdown and oxidation related genes HSL, ATGL, CTP-1, CYP7A1, PPARα mRNA were significantly increased (P < 0.01). Meanwhile, DP regulated the species composition of gut microbiota in obese mice to a certain extent, significantly increased the relative abundance of Blautia, s_unclassified_g_Lachnospiraceae_NK4A136_group, Lachnospiraceae_bacterium_28-4 and Helicobacter rodentium, decreased the relative abundance of Erysipelatoclostridium and Ruminococcus_torques_group, and their dominant strains were positively correlated with fat oxidation and decomposition genes HSL, ATGL, CTP-1, CYP7A1 and PPARα, and negatively correlated with fat synthesis genes FAS, PPARγ and SCD-1. Conclusion DP could significantly reduce the body weight of obese mice induced by a high-fat diet. The mechanism may be related to regulating beneficial bacteria to promote fat oxidation and decomposition and inhibit fat synthesis.

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国家自然科学基金青年项目(82304831);国家自然科学基金面上项目(82274119);河南省自然科学基金优青项目(242300421090);河南省科技研发计划联合基金(优势学科培育类)(232301420077);岐黄学者(国中医药人教函2022-6);河南省国际合作重点项目(231111521200);河南省重点科技计划项目(232301420019);国家中医药管理局联合开放课题(GZYKJS-2022-040-1);河南省高等学校重点科研项目(25CY021);河南省重大公益专项(201300310100)