ObjectiveTo explore the metabolic changes during the differentiation of 3T3-L1 adipocytes caused by the treatment of the transient receptor potential vanilloid 4 (TRPV4)-specific agonist GSK1016790A basing on ultra-performance liquid chromatography-mass spectrometry technology. MethodsMouse 3T3-L1 cells were treated with GSK1016790A at different concentrations (0.1, 1, and 10 μmol/L), and the effect of drugs on cell proliferation was detected by cell counting kit-8 method. A mature adipocyte model was constructed, and GSK1016790A was used to activate TRPV4 channel protein activity and verify the expression levels of TRPV4 and triglycerides. Cell metabolites were collected for metabolomic studies, differential metabolites were screened between groups, and related metabolic pathways were analyzed. Results After GSK1016790A intervened in mature adipocytes, the expression levels of TRPV4 mRNA and triglycerides in cells were significantly upregulated (P<0.05). Metabolomics detection found that GSK1016790A screened a total of 45 differential metabolites such as 2-amino-1,3,4-octadecanetriol, linoleic acid, sphingosine, sphinganine, sn-glycerol-3-phosphate and uridine, mainly involving 13 possible metabolic pathways such as sphingolipid metabolism and biosynthesis of unsaturated fatty acids. Conclusion GSK1016790A may promote adipogenesis in adipocytes by activating TRPV4 channel protein activity, and at the same time participate in regulating metabolic pathways such as the biosynthesis of unsaturated fatty acids pathway and sphingolipid metabolism pathway, affecting lipid metabolism in adipocytes.
ObjectiveTandem mass spectrometry is used to observe the changes in amino acids level in peripheral blood of patients with chronic obstructive pulmonary disease (COPD) of different severity, and explore the related factors that affect the level of amino acids in COPD patients.MethodsA collection of 99 COPD patients from the First Affiliated Hospital of Jinzhou Medical University between May 2020 and August 2020 were divided into GOLD Ⅰ/Ⅱ group, GOLD Ⅲ group and GOLD Ⅳ group according to the results of their lung function. Thirty healthy physical examination subjects during the same period were enrolled as a healthy control group. Peripheral amino acids were detected by liquid chromatography-tandem mass spectrometry (LC-MS).ResultsThe metabolism of 11 amino acids was correlated with the onset of COPD and the disorder of amino acid metabolism became more significant with the aggravation of the disease, and branched-chain amino acids (leucine, valine) had statistically significant differences in the COPD patients with different GOLD grades (P<0.05 and VIP>1). The difference between glutamate and glutamine was statistically significant only in GOLD Ⅳ stage (P<0.05 and VIP>1). The content of tyrosine and phenylalanine gradually increased with the increase of disease severity, and had significant difference in GOLD stage Ⅳ (P<0.05).ConclusionsCOPD patients with different GOLD grades have obvious amino acid metabolism disorders, including insufficient intake of essential amino acids and increased amino acids related to muscle protein catabolism. Understanding the mechanism between amino acid metabolism and COPD may provide a new direction for the diagnosis and treatment of the disease.
ObjectiveTo summarize the research results of metabolites of breast cancer based on metabonomics technology, and systematically reviews them in order to provide a new direction for the research of metabolism of breast cancer.MethodBy searching the relevant literatures in recent years, the application of metabonomics in identifying high-risk breast cancer population, monitoring the progress of tumor and evaluating the response of radiotherapy and chemotherapy were analyzed and summarized.ResultsWith the development of high-resolution, high-sensitivity and high-throughput bioanalysis platform technology, metabolomics had been widely used in breast cancer research field by virtue of its unique perspective and technical advantages to more accurately, systematically and dynamically monitor the changes of host metabolites.ConclusionMetabolomics technology provides a new research direction for primary prevention, early screening and diagnosis of breast cancer and optimal treatment strategy selection.
Objective To explore the effect of corn oligopeptide (COP) on dexamethasone-induced muscle atrophy. Methods Forty-nine male Sprague-Dawley rats aged 8 weeks were divided into blank group (n=10) and model group (n=39). The rats in the model group were intraperitoneally injected with dexamethasone (1.0 mg/kg), and the rats in the blank group were injected with normal saline. After 19 days, one rat in the blank group and three rats in the model group were taken to observe whether the model was successfully constructed. After successful modeling, the rats in the model group were randomly divided into model control group, COP low-dose group (COP-L group, 0.5 g/kg), COP medium-dose group (COP-M group, 1.0 g/kg) and COP high-dose group (COP-H group, 2.0 g/kg), with 9 rats in each group. After 33 days, the grip strength of the rats was measured, and then the gastrocnemius, soleus, tibialis anterior and metatarsal muscles were separated and weighed, and muscle fiber diameter, relative expression of Atrogin-1 and MuRF-1 mRNA were measured. Non-targeted metabolomics of gastrocnemius muscle were measured. Results Compared with that in the blank group, the body weight of rats in the model group reduced (P<0.05), and myofibril rupture was observed, indicating that the model was successful. Compared with those in the model control group, the grip strength increased in the COP-L and COP-M groups (P<0.05); the muscle coefficients of gastrocnemius and soleus in the COP-L and COP-H groups increased (P<0.05), and the muscle coefficients of plantaris in the COP-L and COP-M groups increased (P<0.05); the muscle fiber diameter of the tibial anterior muscle increased in the three doses of COP groups (P<0.05), and the muscle fiber diameter of the plantaris muscle increased in the COP-M and COP-H groups (P<0.05); the relative expression of Atrogin-1 mRNA decreased in the three doses of COP groups (P<0.05), while the relative expression of MurF-1 mRNA in the COP-L and COP-H groups decreased (P<0.05). The amino acid synthesis pathway, glycolysis pathway, and acid metabolism pathway were activated in gastrocnemius muscle. Conclusions COP can significantly improve the muscle atrophy induced by dexamethasone. The mechanism may be related to the decrease of Atrogin-1 and MuRF-1 expression in ubiquitin-proteasome pathway and the increase of amino acid biosynthesis.
Diabetic kidney disease, as a common complication of diabetes, is one of the main causes of end-stage renal disease. Because of the rapid progress of its course and the limited means of treatment, it is of great clinical significance to seek biomarkers from early diagnosis for the treatment of diabetic kidney disease. At present, there are limited methods for early diagnosis of diabetic kidney disease. As a widely used research method, metabonomics can detect metabolites in diseases and provide biomarkers for disease diagnosis and prognosis. This article summarizes the changes of amino acids, lipids, organic acids and other metabolites in blood or urine of patients with diabetic kidney disease.
Objective The method of metabonomics based on nuclear magnetic resonance (NMR) imaging was used to explore the difference in metabolites of serum and bile, and to analyze the metabolic variation related to the pathogenesis of gallbladder stones between normal people/liver transplantation donors and patients with gallbladder stones. Methods Prospectively collected the serum samples (17 cases) and bile samples (19 cases) in 19 patients with gallbladder stones who underwent surgery in West China Hospital form March 2016 to December 2016, as well as the serum samples of 10 healthy persons and the bile samples of 15 liver transplantation donors at the same time period. The differences of metabolites in the blood and bile in these 3 groups were compared by using 1H-NMR metabonomics technology and chemometric methods. Results The concentrations of valine, alanine, lysine, glutamine, glutamate, pyruvate, creatinine, choline, alpha-glucose, beta-glucose, tyrosine, histidine, and hypoxanthine in serum of patients with gallbladder stones decreased significantly, comparing with those of healthy people without gallbladder stones (P<0.05), while 1, 2-propanediol, acetoacetate, and lactate increased significantly in the serum of patients with gallbladder stones (P<0.05). The concentrations of taurine conjugated bile acids, glycine conjugated bile acids, choline, and phosphatidylcholine decreased significantly in the bile of patients with gallbladder stones when compared with those of liver transplantation donors (P<0.05), while cholesterol increased significantly in the bile of patients with gallbladder stones (P<0.05). Conclusions There are significant differences of the serum and bile metabolites between patients with gallbladder stones and healthy men without gallbladder stones/liver transplantation donors. 1H-NMR metabonomics is helpful to investigate the pathogenesis of gallbladder stones.
Inflammatory bowel disease (IBD) is characterized by recurrent abdominal pain, diarrhea, and mucopurulent bloody stools as its main clinical manifestations. In recent years, its parenteral manifestations have received increasing attention. Fatigue, as one of the extraintestinal manifestations of IBD, affects the quality of life of patients, and results in considerable distress for patients. The influencing factors of fatigue symptoms in IBD patients include inflammation, psychological comorbidities, sleep disorders, anemia, micronutrient deficiency, changes in microbiota, and metabolomics. The pathogenesis is currently unclear and may be related to disorders in tryptophan metabolism. This article will review the influencing factors and pathogenesis of fatigue symptoms in IBD patients, aiming to provide a basis for the prevention and treatment of IBD fatigue.
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), and its pathogenesis remains incompletely understood. Research has identified inflammation as a key factor in the onset and progression of DR. As a group of systemic metabolic disorders, the dysregulation of polyunsaturated fatty acid (PUFA) metabolism induced by DM is closely related to the inflammatory mechanisms in DR. Recent metabolomic studies have revealed that in various stages of DR and in diabetic animal models, most upregulated PUFAs and their derivatives act as pro-inflammatory mediators, while downregulated PUFAs and their derivatives are predominantly anti-inflammatory. In the progression of DR, some PUFAs may exert anti-inflammatory effects by inhibiting microglial activation, reducing the expression of inflammatory proteins, antagonizing the pro-inflammatory effects of arachidonic acid, and suppressing the activation of inflammasomes and the migration of neutrophils. Conversely, other PUFAs may promote inflammation through mechanisms such as the formation of pro-inflammatory mediators resembling prostaglandins, facilitating leukocyte adhesion, and inducing oxidative stress responses. PUFAs play a complex dual role in the inflammatory mechanisms of DR. A deeper understanding of these mechanisms not only aids in elucidating the pathogenesis of DR but also provides potential targets for developing new therapeutic strategies.
Objective To analyze the metabolic characteristics of myocardial infarction (MI) using metabolomics to better understand its pathogenesis and to explore new therapeutic directions for MI. Methods Serum metabolites in ten acute MI mice and five sham-control mice were analyzed by UHPLC-QqQ/MS, and SPSS was used for statistical analysis. MetaboAnalyst 5.0 was used to analyze the metabolic pathways of the differential metabolites and build a metabolic network. Results One hundred and twenty-nine metabolites were detected by UHPLC-QqQ/MS. Significant serum metabolite differences were found between MI mice and normal controls. Fifty out of 129 metabolites in serum were associated with MI. In addition, the most important metabolic pathways were D-glutamate metabolism, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate acid metabolism. ConclusionMetabolites in serine-related metabolic pathways reduce in serum in MI. We propose a new therapeutic direction for myocardial protection in MI.