UPLC-Q-TOF/MS based metabolomic profiling of serum and urine of hyperlipidemic rats induced by high fat diet

Wu, Qiong; Hai, Zhang; Dong, Xin; Chen, Xiaofei; Zhu, Zhenyu; Hong, Zhanying; Chai, Yifeng

doi:10.1016/j.jpha.2014.04.002

Cited by 34 publications

(17 citation statements)

References 35 publications

(49 reference statements)

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“…Because glycolysis is suppressed and gluconeogenesis is upregulated in the HFD group [ 36 ], monosaccharides were anticipated to increase in the urine of the HFD group. In previous findings, the alteration of pseudouridine, creatinine, taurine, and hippuric acid levels in HFD group showed similar patterns when compared to our results [ 36 , 37 ]. According to one study, HFD intake was related to an increase in lipid oxidation, lipid accumulation, and changes in choline, purine, and amino acid metabolism.…”

Section: Resultssupporting

confidence: 90%

“…Many researchers also suggest that the alteration of gut microbiota by HFD exacerbates inflammation and obesity [ 30 , 32 ]. Hippuric acid is derived from phenylalanine, and its metabolite is represented in a lower proportion in the urine of the HFD group due to the modulation of the gut microbiota population [ 37 ]. The results of the comparison of GC-TOF-MS results in the ND and HFD group suggested that the alteration of these metabolites was associated with overall metabolic dysfunction.…”

Section: Resultsmentioning

confidence: 99%

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Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

et al. 2015

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Abstract:In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit OPEN ACCESSMolecules 2015, 20 3108 HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

et al. 2015

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“…This might be due to disturbed gut microbiota metabolism under diabetic status [ 70 ]. As reported, concentrations of hippuric acid were lower in HFD-induced hyperlipidemic rats than in normal rats [ 71 ]. d -glucurono-6,3-lactone, participating in ascorbate and aldarate metabolism, was increased in T2DM rats and was downregulated after treatment of SR, CR and their combined extracts.…”

Section: Discussionmentioning

confidence: 72%

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Cui

Qian

Jiang

et al. 2018

IJMS

174

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Aim Scutellariae Radix (SR) and Coptidis Rhizoma (CR) have often been combined to cure type 2 diabetes mellitus (T2DM) in the clinical practice for over thousands of years, but their compatibility mechanism is not clear. Mitogen-activated protein kinase (MAPK) signaling pathway has been suggested to play a critical role during the process of inflammation, insulin resistance, and T2DM. This study was designed to investigate their compatibility effects on T2DM rats and explore the underlying mechanisms by analyzing the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Methods The compatibility effects of SR and CR were evaluated with T2DM rats induced by a high-fat diet (HFD) along with a low dose of streptozocin (STZ). Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers. The levels of pro-inflammatory cytokines; biochemical indexes in serum, and the activities of key enzymes related to glycometabolism in liver were assessed by ELISA kits. qPCR was applied to examine mRNA levels of key targets in MAPK and insulin signaling pathways. Protein expressions of p65; p-p65; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K); phosphorylated-PI3K (p-PI3K); protein kinase B (Akt); phosphorylated Akt (p-Akt) and glucose transporter 2 (Glut2) in liver were investigated by Western blot analysis. Results Remarkably, hyperglycaemia, dyslipidemia, inflammation, and insulin resistance in T2DM were ameliorated after oral administration of SR and CR, particularly their combined extracts. The effects of SR, CR, low dose of combined extracts (LSC) and high dose of combined extracts (HSC) on pro-inflammatory cytokine transcription in T2DM rats showed that the MAPK pathway might account for the phenomenon with down-regulation of MAPK (P38 mitogen-activated protein kinases (P38), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK)) mRNA, and protein reduction in p-P65. While mRNA levels of key targets such as insulin receptor substrate 1 (IRS1), PI3K, Akt2, and Glut2 in the insulin signaling pathway were notably up-modulated, phosphorylations of PI3K, Akt, and expression of Glut2 were markedly enhanced. Moreover, the increased activities of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase), and glycogen phosphorylase (GP) were highly reduced and the decreased activities of glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK), and glycogen synthase (GS) in liver were notably increased after treatment. Further investigation indicated that the metabolic profiles of plasma and urine were clearly improved in T2DM rats. Fourteen potential biomarkers (nine in plasma and five in urine) were identified. After intervention, these biomarkers returned to normal level to some extent. Conclusion The results showed that SR, CR, and combined extract groups were normalized. The effects of combined extracts were more remarkable than single herb treatm...

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“…Biochemical parameters including total bilirubin (T-BIL), total protein (TP), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glucose (GLU), triglycerides (TG) and total cholesterol (TCH), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL), were analyzed in the experiment. The AI was calculated as followed: AI = (TCH - HDL)/HDL 24 . The kits for biochemistry analysis were provided by Ningbo Medical System Biotechnology Co., Ltd (Ningbo, China).…”

Section: Methodsmentioning

confidence: 99%

UPLC-Q-TOF/MS-based metabonomic studies on the intervention effects of aspirin eugenol ester in atherosclerosis hamsters

Yang

Liu

et al. 2017

Sci Rep

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Based on the pro-drug principle, aspirin and eugenol were used to synthesize aspirin eugenol ester (AEE) by esterification reaction. In present study, the anti-atherosclerosis effects of AEE were investigated in hamsters with the utilization of metabonomic approach based on UPLC-Q-TOF/MS. Biochemical parameters and histopathological injures in stomach, liver and aorta were evaluated. In atherosclerotic hamster, oral administration of AEE normalized biochemical profile such as reducing TG, TCH and LDL, and significantly reduced body weight gain, alleviated hepatic steatosis and improved pathological lesions in aorta. Slight damages in stomach mucous were found in AEE group. Plasma and urine samples in control, model and AEE groups were scattered in the partial least squares-discriminate analysis (PLS-DA) score plots. Thirteen endogenous metabolites in plasma such as lysophosphatidylcholine (LysoPC), leucine and valine, and seventeen endogenous metabolites in urine such as citric acid, phenol sulphate and phenylacetylglycine were selected as potential biomarkers associated with atherosclerosis. They were considered to be in response to anti-atherosclerosis effects of AEE, mainly involved in glycerophospholipid metabolism, amino acid metabolism and energy metabolism. This study extended the understanding of endogenous alterations of atherosclerosis and offered insights into the pharmacodynamic activity of AEE.

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UPLC-Q-TOF/MS based metabolomic profiling of serum and urine of hyperlipidemic rats induced by high fat diet

Cited by 34 publications

References 35 publications

Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

UPLC-Q-TOF/MS-based metabonomic studies on the intervention effects of aspirin eugenol ester in atherosclerosis hamsters

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