| Metabolic syndrome(MS)is a series of complicated disease states related to metabolic abnormalities,and has become a worldwide public health problem endangering people’s health.The definition of MS is diversified and its pathogenesis is complicated,which has not been fully elucidated yet.Therefore,the in-depth study on the pathological mechanism of metabolic syndrome has promising potential for its prevention and treatment.The metabolic syndrome induced by monosodium glutamate(MSG)is dominated by abdominal obesity.MSG causes neuronal necrosis in the hypothalamus,leading to endocrine and other dysfunctions,and ultimately inducing metabolic disorders,which is the mainly reported mechanism up to now.However,it is unclear whether the gut microbiota,which plays an important role in the occurrence and development of metabolic diseases and in the gut-brain axis,is involved in the MSG-induced hypothalamic damage.Quercetin is a kind of flavonoids widely existing in people’s diet,which has the effects on lowering blood lipid,reducing blood glucose,and anti-inflammatory.Its clinical application is becoming increasingly extensive,but whether quercetin can improve MSG-induced metabolic syndrome needs further research.In this study,we prepared the MSG-induced metabolic syndrome model characterized by abdominal obesity.16 S ribosomal DNA(16S r DNA)sequencing technology was used to analyze changes in gut microbiota to explore the role of gut microbiota in MSG-induced metabolic syndrome,and the pathological mechanism of MSG-induced metabolic syndrome at the molecular level was investigated by transcriptomics methods and verified by experiments.On this basis,the therapeutic effect and mechanism of quercetin on MSG-induced metabolic syndrome were studied.Main results are as follows:(1)Subcutaneous injection of MSG(3 mg/g)into neonatal mice for inducing neuronal damage at the arcuate nucleus of hypothalamus,resulting in abdominal obesity,lipids and glucose metabolism disorders in mice.The results of fecal 16 S r DNA sequencing showed that the structure of gut microbiota in MSG-treated mice was significantly changed.Compared with control group,the ratio of Firmicutes to Bacteroidetes increased significantly,and the relative abundance of Akkermansia and Prevotella decreased significantly.After depleting gut microbiota via antibiotics intervention,MSG-induced abdominal obesity,glucose and lipid metabolism disorder and other metabolic syndromes disappeared.Co-house study showed that the structure of the gut microbiota in MSG-treated mice was very close to that of the gut microbiota in the control mice via ingesting the feces of control mice.Among them,the ratio of Firmicutes to Bacteroidetes notably decreased,and the relative abundance of Akkermansia and Prevotella notably increased.In addition,the intestinal barrier function of MSG-treated mice was enhanced after co-house.Moreover,the metabolic syndrome characteristics such as abdominal obesity,glucose and lipid metabolism disorder were improved,indicating that the gut microbiota played an important regulatory role in MSG-induced metabolic syndrome.(2)The results of liver transcriptomics pathway analysis showed that MSG upregulated genes related to epoxygenase P450 pathway,oxidation-reduction process,cell death and so on,while down-regulated genes related to lipid metabolism,heat production,glucose metabolism,insulin secretion,etc.Heatmap analysis of differentially expressed genes showed that MSG significantly increased the expression level of retinol saturase(Ret Sat).PCR results showed that the expression level of transcription factor peroxisome proliferator-activated receptor-α(PPAR-α),the master regulator of Ret Sat,also remarkably increased.After small interfering RNA(si RNA)down-regulated Ret Sat in hepatocytes of MSG-treated group,the expression levels of lipid synthesis-related genes markedly decreased,indicating that MSG mainly induced the high expression of Ret Sat mediated by PPAR-α to promote lipid synthesis in the liver.Whereas,there was no difference at the expression level of Ret Sat between the two groups of mice treated with antibiotics,but it was significantly lower than that of the control group;after co-house,the expression level of Ret Sat in MSG-treated mice decreased significantly,indicating that the gut microbiota can regulate the expression of Ret Sat.In addition,the expression level of bile acid,which has an inhibitory effect on liver PPAR-α,decreased in MSG-treated mice,but increased after co-house,indicating that the gut microbiota may affect liver lipid synthesis through bile acid metabolism.(3)Fecal 16 S r DNA sequencing results showed that after treatment with quercetin(5mg/kg)for 6 weeks,the structure of the gut microbiota in MSG-treated mice was significantly changed,the ratio of Firmicutes to Bacteroidetes significantly decreased,and the relative abundance of Bacteroides increased,indicating that quercetin can improve the gut microbiota dysbiosis in MSG-treated mice.Moreover,the intestinal barrier function of MSG-treated mice was improved,and the level of intestinal inflammation decreased;the levels of bile acid synthase and bile acid in the liver increased after treatment with quercetin.Transcriptomics analysis showed that the expression level of Ret Sat was significantly reduced.Abdominal obesity,glucose and lipid metabolism disorders and other metabolic syndrome characteristics have also been improved.In conclusion,this study explored the pathogenesis of MSG-induced metabolic syndrome,and found that MSG could cause gut microbiota dysbiosis,leading to abdominal obesity,lower bile acid level and higher hepatic lipogenesis,and ultimately induce metabolic syndrome.Besides,quercetin reduced abdominal obesity,increased liver bile acid levels,and reduced lipid synthesis by modulating the gut microbiota,thereby improving MSG-induced metabolic syndrome.These studies provide new explanation to the pathogenesis of MSG-induced metabolic syndrome and a reference for drug treatment of metabolic syndrome. |
PDF Full Text Request