Dataset Information

Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveals Novel Insights for Metabolic Alterations in the Disease Pathogenesis

ABSTRACT: The pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct LC-MS/MS based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over time with a boost in expression were enriched in lipase activity, lipoprotein and lipids absorption and transport regulation. Furthermore, 16 proteins associated with lipid metabolism and signaling pathways together with the whole lipid species changing profile led to the vital identification of changing law in glycerides, phosphoglycerides and free fatty acids. In addition to lipid metabolism and regulation associated proteins, several digestive enzymes and adaptive anti-trypsin, stress response, and energy metabolism related proteins showed an increment in abundance. Notably, central carbon and branched chain amino acids metabolism were enhanced during 0-24 h from the first cerulein stimulation. Taken together, this integrated proteomics and lipidomics revealed a novel metabolic insight on metabolites transforming rules that might be relevant to their function and drug targets investigation.

ORGANISM(S): Mus Musculus

SUBMITTER: Dan Du

PROVIDER: PXD038567 | iProX | Tue Dec 06 00:00:00 GMT 2022

REPOSITORIES: iProX

ACCESS DATA

Publications

Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveal Novel Insights for Metabolic Alterations in the Disease Pathogenesis.

Wang Rui R Wang Yiqin Y Tao Yiran Y Hu Liqiang L Qiu Qi Q Pu Qianlun Q Yang Juqin J Wang Shisheng S Huang Yan Y Chen Xiaoting X Zhu Ping P Yang Hao H Xia Qing Q Du Dan D

ACS omega 20230321 13

The pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct liquid chromatography-mass spectrometry (LC-MS/MS)-based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over ...[more]

PMID: 37033809

Similar Datasets

Project description:Gupta2009 - Eicosanoid Metabolism Integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis. This model is described in the article: An integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis. Gupta S, Maurya MR, Stephens DL, Dennis EA, Subramaniam S. Biophys. J. 2009 Jun; 96(11):4542-51. Abstract: There is increasing evidence for a major and critical involvement of lipids in signal transduction and cellular trafficking, and this has motivated large-scale studies on lipid pathways. The Lipid Metabolites and Pathways Strategy consortium is actively investigating lipid metabolism in mammalian cells and has made available time-course data on various lipids in response to treatment with KDO(2)-lipid A (a lipopolysaccharide analog) of macrophage RAW 264.7 cells. The lipids known as eicosanoids play an important role in inflammation. We have reconstructed an integrated network of eicosanoid metabolism and signaling based on the KEGG pathway database and the literature and have developed a kinetic model. A matrix-based approach was used to estimate the rate constants from experimental data and these were further refined using generalized constrained nonlinear optimization. The resulting model fits the experimental data well for all species, and simulated enzyme activities were similar to their literature values. The quantitative model for eicosanoid metabolism that we have developed can be used to design experimental studies utilizing genetic and pharmacological perturbations to probe fluxes in lipid pathways. This model is hosted on BioModels Database and identified by: BIOMD0000000436 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and can rapidly progress to non-alcoholic steatohepatitis (NASH). Accurate preclinical models and robust methodologies need to be established to understand the underlying metabolic mechanisms and develop treatment strategies. Based on our meta-analysis of currently available data on several mouse models, we hypothesized a diet- and chemical-induced NASH model closely resembles metabolic alteration in human. We developed an already established WD+CCl4-induced NASH model. We developed and performed transcriptomics driven metabolic pathway analysis (TDMPA) using differentially expressed genes in mouse NASH liver compared to control. We compared the altered metabolic pathways and enzymatic reactions to human NASH. We performed functional assays and lipidomics to confirm our findings related to metabolic alterations. Numerous metabolic pathways were altered in human NASH and mouse model. De novo triglyceride biosynthesis, fatty acid beta-oxidation, bile acid biosynthesis, cholesterol metabolism, and oxidative phosphorylation were the most influenced pathways. We confirmed significant reduction in mitochondrial functions and bioenergetics in NASH model, and in acylcarnitines. We identified a wide range of lipid species within the most perturbed pathways predicted by TDMPA. Triglycerides, phospholipids and bile acids were increased significantly in NASH, confirming our initial observations. We identified several metabolic pathways that typify NASH pathophysiology in human. By comparing human and mouse metabolic signatures, we evaluated metabolic resemblance of mouse model to human and its suitability for the study of the disease and potential usage for drug discovery and testing. We also presented TDMPA, a novel methodology to evaluate metabolic pathway alterations in metabolic disorders and a valuable tool for defining metabolic space to aid experimental design for lipidomics and metabolomics approaches.

Dataset Information

Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveals Novel Insights for Metabolic Alterations in the Disease Pathogenesis

Publications

Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveal Novel Insights for Metabolic Alterations in the Disease Pathogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure