Dataset Information

Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

ABSTRACT: Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.

SUBMITTER: Zhou P

PROVIDER: S-EPMC6479315 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

Zhou Peipei P Yang Xiaolin X Yang Zhonglin Z Huang Wenzhe W Kou Junping J Li Fei F

Molecules (Basel, Switzerland) 20190401 7

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemic ...[more]

PMID: 30939835

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Project description:To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE) and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD) rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1) The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group) (P<0.05). (2) Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05). TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05). (3) mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05), as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05). The activities of these enzymes also paralleled the observed changes in mRNA levels. (4) There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1) the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2) the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

Project description:PURPOSE:Obesity, a worldwide health problem, is linked to an abnormal gut microbiota and is currently most effectively treated by bariatric surgery. Our aim was to characterize the microbiota of high-fat fed Sprague-Dawley rats when subjected to bariatric surgery (i.e., vertical sleeve gastrectomy) and posterior refeeding with either a high-fat or control diet. We hypothesized that bariatric surgery followed by the control diet was more effective in reverting the microbiota modifications caused by the high-fat diet when compared to either of the two factors alone. METHODS:Using next-generation sequencing of ribosomal RNA amplicons, we analyzed and compared the composition of the cecal microbiota after vertical sleeve gastrectomy with control groups representing non-operated rats, control fed, high-fat fed, and post-operative diet-switched animals. Rats were fed either a high-fat or control low-fat diet and were separated into three comparison groups after eight weeks comprising no surgery, sham surgery, and vertical sleeve gastrectomy. Half of the rats were then moved from the HFD to the control diet. Using next-generation sequencing of ribosomal RNA amplicons, we analyzed the composition of the cecal microbiota of rats allocated to the vertical sleeve gastrectomy group and compared it to that of the non-surgical, control fed, high-fat fed, and post-operative diet-switched groups. Additionally, we correlated different biological parameters with the genera exhibiting the highest variation in abundance between the groups. RESULTS:The high-fat diet was the strongest driver of altered taxonomic composition, relative microbial abundance, and diversity in the cecum. These effects were partially reversed in the diet-switched cohort, especially when combined with sleeve gastrectomy, resulting in increased diversity and shifting relative abundances. Several highly-affected genera were correlated with obesity-related parameters. CONCLUSIONS:The dysbiotic state caused by high-fat diet was improved by the change to the lower fat, higher fiber control diet. Bariatric surgery contributed significantly and additively to the diet in restoring microbiome diversity and complexity. These results highlight the importance of dietary intervention following bariatric surgery for improved restoration of cecal diversity, as neither surgery nor change of diet alone had the same effects as when combined.

Dataset Information

Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

Publications

Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

Similar Datasets

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