槲皮素对高脂饮食诱导肥胖小鼠肝脏脂肪变性的改善作用及对色氨酸代谢物的影响

Quercetin Ameliorates Hepatic Steatosis and Influences Tryptophan Metabolites in Obese Mice Induced by a High-fat Diet

摘要:

探讨槲皮素干预通对高脂饮食诱导肥胖小鼠肝脏脂肪变性的改善作用及对色氨酸代谢物的影响。该实验采用高脂饮食建立肥胖小鼠模型。将雄性C57BL/6J小鼠随机分为对照组（NC）、模型组（HFD）和槲皮素干预组（HFD+Q），每组10只。HFD+Q组小鼠灌胃给予槲皮素（50 mg/kg.BW），持续16周。称量小鼠体质量和肝脏组织的质量；组织切片和油红O染色检测肝脏脂肪沉积情况，ELISA检测丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆固醇（TC）、三酰甘油（TG）水平；qPCR检测炎症因子白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）以及脂质代谢相关基因脂肪酸合成酶（FAS）、固醇调节元件结合蛋白1c（SREBP-1c）和ATP结合盒转运体A1（ABCA1）等基因的相对表达量；LC-MS技术靶向分析血清中色氨酸代谢产物吲哚-3-乙酸（IAA）和吲哚-3-丙酸（IPA）的含量。槲皮素干预能显著减少肥胖小鼠的体质量增加（P<0.05），减少肝脏脂肪沉积，降低炎症因子TNF-α（62.96%）、IL-1β（42.52%）和IL-6（50.88%）mRNA表达水平，抑制FAS（80.36%）、SREBP-1c（23.54%），提高ABCA1（5.21倍）脂质代谢基因mRNA表达；增加色氨酸代谢物IAA（1.71倍）和IPA（1.12倍）的含量。结论提示，槲皮素可减少肝脏脂肪沉积，减少肝脏炎性因子的表达，改善高脂饮食诱导的肥胖小鼠肝脏脂肪变性，同时增加血清中吲哚-3-乙酸、吲哚-3-丙酸等色氨酸代谢物含量。

Abstract:

The purpose of this study was to investigated the ameliorating effect of quercetin on liver steatosis and its influence on tryptophan metabolites in obese mice induced by a high-fat diet. The obese mouse model was established using a high-fat diet. Male C57BL/6J mice were randomly divided into a control group (NC), a model group (HFD) and a quercetin intervention group (HFD+Q), with 10 mice in each group. The mice in the HFD+Q group were given 50 mg/kg.BW quercetin by gavage for 16 weeks. The body weights and liver weights of mice were measured. Fat deposition in the liver was detected tissue sections and oil red O staining. The ALT, AST, TC and TG levels were determined by ELISA. The relative expression levels of inflammatory cytokines, IL-1β, TNF-α and IL-6, and lipid metabolism-related genes, FAS, SREBP-1c and ABCA1, in the liver were determined by qPCR. The contents of serum tryptophan metabolites, indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA), were determined by LC-MS targeted analysis. Quercetin intervention significantly (P<0.05) decreased the HFD-induced body weight gain, liver steatosis, and the levels of IL-6 (50.88%), IL-1β (42.52%), TNF-α (62.96%), FAS (80.36%) and SREBP-1c (23.54%), whilst increasing the mRNA expression level of ABCA1 (5.21 times) and the contents of tryptophan metabolites, indole-3-acetic acid (1.71 times) and indole-3-propionic acid (1.12 times). In conclusion, quercetin can reduce liver fat deposition, decrease the expression of inflammatory factors in the liver, ameliorate HFD-induced hepatic steatosis in obese mice, while increasing the contents of serum tryptophan metabolites such as indole-3-acetic acid and 3-indolepropionic acid.