Proteomics Analysis Provides Insights into the Role of Lipid Metabolism in T2DM-Related Sarcopenia
Jingying WuShengnan WangHuafeng ZhuangWei WangYaoguo WangYoufang ChenZhengping HuangChunnuan ChenXiaofeng Chen
1
Citation
36
Reference
10
Related Paper
Citation Trend
Abstract:
Sarcopenia has been recognized as an emerging complication of type 2 diabetes mellitus (T2DM). Currently, the pathogenesis of T2DM-related sarcopenia remains unclear. The aim of this study was to investigate the molecular mechanisms and potential therapeutic targets for T2DM-related sarcopenia. In this study, a T2DM-related sarcopenia mouse model was established using db/db mice. Proteins extracted from the gastrocnemius muscles of db/db mice and littermate control db/m mice were analyzed by a 4D label-free quantitative proteomics approach. A total of 131 upregulated and 68 downregulated proteins were identified as differentially expressed proteins (DEPs). Bioinformatics analysis revealed that DEPs were significantly enriched in lipid metabolism. Protein-protein interaction network analysis revealed that six hub proteins, including ACOX1, CPT2, ECI2, ACADVL, ACADL, and ECH1, were involved in the fatty acid oxidation. The hub protein-transcription factor-miRNA network was also constructed using the NetworkAnalyst tool. Finally, the hub proteins were validated by Western blotting and immunohistochemistry and further confirmed to be significantly negatively correlated with muscle mass and grip strength. Our study suggested that lipid metabolism, especially excessive fatty acid oxidation, may be a crucial contributor to the progression of T2DM-related sarcopenia and a common cause of the inter-relationship between T2DM and sarcopenia. Targeting lipid metabolism may be a promising therapeutic strategy for T2DM-related sarcopenia.Keywords:
Carbohydrate Metabolism
Fatty Acid Metabolism
Fatty Acid Metabolism
Cite
Citations (0)
Carbohydrate Metabolism
Fatty Acid Metabolism
Coenzyme A
Cite
Citations (6)
Carbohydrate Metabolism
Indinavir
Ritonavir
Cite
Citations (32)
Carbohydrate Metabolism
Indinavir
Ritonavir
Cite
Citations (49)
Obesity is an emerging health problem in world wide countries. High fat diet (HFD), which is the main cause of obesity, induces inflammation and affects both lipid and carbohydrate metabolism. This study investigates the effect of inflammation induced by HFD on lipid and carbohydrate metabolism. This study involves two parts, in vivo and in vitro. In the in vivo part, adult male albino rats were fed a HFD for 8 and 14 weeks. After each feeding period, the following parameters were measured (body weight, blood glucose levels, oral glucose tolerance, serum insulin, insulin resistance, total cholesterol, HDLc, LDLc, triglycerides, free fatty acids, neutrophils percentage and serum CRP levels) in addition to pancreas tissue histopathology. In the in vitro part, insulin release from isolated perfused pancreas preparations was measured. Pancreas preparations were isolated from adult male albino rats fed a HFD for 16 weeks. Feeding rats a HFD for 8 and 14 weeks induced inflammation, impaired lipid profile and carbohydrate metabolism. Feeding rats a HFD for 16 weeks increased in vitro glucose-stimulated insulin release. HFD induces inflammation which plays an important role in the impairment of lipid and carbohydrate metabolism.
Carbohydrate Metabolism
Lipid Profile
Cite
Citations (2)
Fatty Acid Metabolism
Carbohydrate Metabolism
Adenosine triphosphate
Cite
Citations (2)
Berberine has been reported to modulate glucose and lipid metabolism in the body.This review was renewed its reported beneficial effect in insulin secretion and insulin signaling pathway,glucose transport and metabolism,low density lipoprotein receptor,AMP kinase activity,adipocytes differentiation,lipid and energy metabolism,and attempted to discuss the mechanisms of berberine in regulating glucose and lipid metabolism and its joint regulation,which indicated the clinical application prospects and problems of berberine.
Carbohydrate Metabolism
Cite
Citations (0)
Carbohydrate Metabolism
Cite
Citations (5)
Carbohydrate Metabolism
Cite
Citations (102)
To illustrate the metabolic regulatory mechanisms of Jiangzhi decoction (JZD) against non-alcoholic fatty liver disease (NAFLD).High-fat diet (HFD)-induced NAFLD rats were treated with JZD. The pathological morphology, lipid indexes and liver function were detected. Metabolic profiles were examined by liquid chromatography-mass spectrometry (LC-MS). Multivariate and univariate statistical analysis were used to search the differential metabolites. Pathway enrichment analysis was carried out using Kyoto Encyclopedia of Genes and Genomes database. Compound-gene networks were built by Cytoscape software.JZD significantly alleviated the pathological conditions and improved lipid index levels. Multivariate analysis showed a good separation among different groups. Three hundred and twenty-seven metabolites in HFD versus control and 301 metabolites in JZD versus HFD were identified to be significantly different. Pathway enrichment analysis showed that lipid metabolism pathways were prominent altered pathways. Importantly, the relationships were more distant between JZD and HFD groups in all five lipid metabolism pathways, including arachidonic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism and sphingolipid metabolism, while those were obviously closer between JZD and control groups. Simultaneously, JZD treatment restored the levels of disturbed differential metabolites in HFD group.JZD had an effect on alleviating NAFLD via regulating relevant lipid metabolism.
Glycerophospholipids
Metabolic pathway
Fatty Acid Metabolism
KEGG
Decoction
Sphingolipid
Cite
Citations (4)