Serum untargeted metabolomics analysis of the mechanisms of evodiamine on type 2 diabetes mellitus model rats

Yu, Yuejie; Lu, Qinyan; Chen, Feng; Wang, Shangli; Niu, Chunxiang; Liao, Jiabao; Wang, Hongwu; Chen, Fengjuan

doi:10.1039/d1fo04396j

Cited by 22 publications

(9 citation statements)

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“…Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to screen differential metabolic pathways based on the following conditions: pathway impact >0.1 and P < 0.05 ( 13 ). As shown in Figures 6A, B , the following 14 metabolic pathways were identified in SADI-S group: tryptophan metabolism; cysteine and methionine metabolism; phenylalanine metabolism; phenylalanine; tyrosine and tryptophan biosynthesis; arginine biosynthesis; alanine, aspartate and glutamate metabolism; Arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; alpha-Linolenic acid metabolism; Linoleic acid metabolism; riboflavin metabolism; nicotinate and nicotinamide metabolism; pyrimidine metabolism; porphyrin and chlorophyll metabolism.…”

Section: Resultsmentioning

confidence: 99%

Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal–ileal bypass with sleeve gastrectomy

Wang

et al. 2022

Front. Endocrinol.

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BackgroundSingle-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known.ObjectiveTo explore the effects of SADI-S on metabolites in the stool of rats with T2DM.MethodsTwenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry.ResultsAt 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups. Among them, 16 metabolites such as branched-chain amino acids (valine), aromatic amino acid (phenylalanine), bile acid (cholic acid, lithocholic acid, and β-muricholic acid), short-chain fatty acid (isobutyric acid), and phospholipid [lysoPE(17:0), lysoPE(20:3) and lysoPS(16:0)] were associated to the T2DM remission after SADI-S.ConclusionSADI-S improves T2DM in rats by regulating phenylalanine biosynthesis, valine, phenylalanine, alanine, glutamate, proline, bile acid, and phospholipid metabolism pathways.

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Section: Resultsmentioning

confidence: 99%

Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal–ileal bypass with sleeve gastrectomy

Wang

et al. 2022

Front. Endocrinol.

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“…Arginine is proposed to be the largest nitrogen-donating amino acid in the body and acts as the precursor of proline. Arginine metabolism has been found to affect multiple processes including amino acid synthesis and the regulation of immune functions, and is also closely related to the progression of T2D [ 42 ]. In consistency with these metabolic changes, the insulin and PI3K-Akt signaling pathways were also substantially enhanced in the liver of the HF mice with CLA supplemented.…”

Section: Discussionmentioning

confidence: 99%

Conjugated Linoleic Acid Ameliorates High Fat-Induced Insulin Resistance via Regulating Gut Microbiota–Host Metabolic and Immunomodulatory Interactions

Wu,

Ye,

Deng

et al. 2024

Nutrients

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Interaction between gut microbiota, host immunity and metabolism has been suggested to crucially affect the development of insulin resistance (IR). This study aims to investigate how gut microbiota, inflammatory responses and metabolism in individuals with IR are affected by the supplementation of conjugated linoleic acid (CLA) and how this subsequently affects the pathophysiology of IR by using a high-fat diet-induced IR mouse model. Serum biochemical indices showed that 400 mg/kg body weight of CLA effectively attenuated hyperglycemia, hyperlipidemia, glucose intolerance and IR, while also promoting antioxidant capacities. Histomorphology, gene and protein expression analysis revealed that CLA reduced fat deposition and inflammation, and enhanced fatty acid oxidation, insulin signaling and glucose transport in adipose tissue or liver. Hepatic transcriptome analysis confirmed that CLA inhibited inflammatory signaling pathways and promoted insulin, PI3K-Akt and AMPK signaling pathways, as well as linoleic acid, arachidonic acid, arginine and proline metabolism. Gut microbiome analysis further revealed that these effects were highly associated with the enriched bacteria that showed positive correlation with the production of short-chain fatty acids (SCFAs), as well as the improved SCFAs production simultaneously. This study highlights the therapeutic actions of CLA on ameliorating IR via regulating microbiota–host metabolic and immunomodulatory interactions, which have important implications for IR control.

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“…This phenomenon may be related to chronic inflammation, which upregulates the activity of tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase, the rate-limiting enzymes in the conversion of tryptophan to kynurenine ( 73 ). 3-HAA, one of the downstream products of L-kynurenine, exhibits anti-inflammatory and lipid-regulating functions ( 74 , 75 ). 5-HT is one of the intermediates of the serotonin metabolic pathway, and its conversion to 5-hydroxyindoleacetic acid is accelerated when serum tryptophan levels are reduced in patients with T2DM, which may contribute to the reduced levels of 5-HT ( 76 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats

Ma,

Sun,

Wang

et al. 2023

Front. Endocrinol.

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IntroductionYu–Ye Tang (YYT) is a classical formula widely used in treatment of type 2 diabetes mellitus (T2DM). However, the specific mechanism of YYT in treating T2DM is not clear.MethodsThe aim of this study was to investigate the therapeutic effect of YYT on T2DM by establishing a rat model of T2DM. The mechanism of action of YYT was also explored through investigating gut microbiota and serum metabolites.ResultsThe results indicated YYT had significant therapeutic effects on T2DM. Moreover, YYT could increase the abundance of Lactobacillus, Candidatus_Saccharimonas, UCG-005, Bacteroides and Blautia while decrease the abundance of and Allobaculum and Desulfovibrio in gut microbiota of T2DM rats. Nontargeted metabolomics analysis showed YYT treatment could regulate arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine metabolism, steroid hormone biosynthesis, terpenoid backbone biosynthesis, tryptophan metabolism, and tyrosine metabolism in T2DM rats.DiscussionIn conclusion, our research showed that YYT has a wide range of therapeutic effects on T2DM rats, including antioxidative and anti-inflammatory effects. Furthermore, YYT corrected the altered gut microbiota and serum metabolites in T2DM rats. This study suggests that YYT may have a therapeutic impact on T2DM by regulating gut microbiota and modulating tryptophan and glycerophospholipid metabolism, which are potential key pathways in treating T2DM.

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Serum untargeted metabolomics analysis of the mechanisms of evodiamine on type 2 diabetes mellitus model rats

Abstract: Evodiamine (EVO) is an alkaloid extracted from Evodia rutaecarpa and has various pharmacological activities, including hypolipidemic, anti-inflammatory, anti-infective, and antitumor effects. However, the therapeutic effects of EVO on type 2...

Cited by 22 publications

References 88 publications

Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal–ileal bypass with sleeve gastrectomy

Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal–ileal bypass with sleeve gastrectomy

Conjugated Linoleic Acid Ameliorates High Fat-Induced Insulin Resistance via Regulating Gut Microbiota–Host Metabolic and Immunomodulatory Interactions

Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats

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