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Vinyl chloride altered pancreas proteome and pathways associated with metabolism and predisposed mouse to enhanced metabolic stress
Citation:
Ge, Y., M. Bruno, M. Nash, N. Haykal-Coates, B. Chorley, M. Cave, AND J. Beier. Vinyl chloride altered pancreas proteome and pathways associated with metabolism and predisposed mouse to enhanced metabolic stress. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 193(1):103-114, (2023). https://doi.org/10.1093/toxsci/kfad024
Impact/Purpose:
Abnormal pancreatic function can result from environmental exposures, such as chemicals and diet, which can impact susceptibility to metabolic problems and fatty diseases. It has been reported that environmental vinyl chloride (VC) exposure significantly increased steatosis in mice fed a high?fat diet (HFD) but not low-fat diet (LFD). However, little is known about toxicity pathways, key pathway regulators, and molecular mechanisms underlying the VC-increased steatosis and environmental susceptibility. The present study was undertaken to examine the protein responses to VC exposure at a low concentration of 0.1 ppm for 12 weeks in pancreas tissues of six-week-old C57BL/6J mice fed LFD or HFD using a combination of mouse cytokine array and Western blot, with a focus on the investigation of the changes at expression and/or phosphorylation levels of some cytokines and protein biomarkers involved in steatosis and related metabolomic disorders or diseases. The proposed work is housed under the Research Action Plan supporting work proposed in Chemical Safety for Sustainability (CSS) , Adverse Outcome Pathways Discovery and Development (AOPDD). Specifically, the investigations conducted are meant to cover the QA requirements of AOPDD Tasks for Putative AOP development related to fatty liver disease (steatosis) and other tissues such as pancreas and lungs. Work under this task will also broadly support CSS AOP-DD Key Products, in addition to goals outlined in Tasks such as Expert knowledge approach to putative AOP development, Bioinformatic approach to putative AOP development, Taxonomic relevance of AOPs, Putative AOP development - cancer, AOP knowledge-base development, ADME module and considerations in AOP application, and AOP network application case studies. While much of the work is based in CCTE, interdisciplinary collaborations with Program Offices (OCSPP, OW, others) as well as extramural collaboration with academic, governmental and applied industry --will develop and apply chemical evaluation strategies and design of decision-support tools. The pAOPnet for cumulative risks of HFD and VC will immediately improve the agency's scientific knowledge of combined chemical exposures and high caloric food intake leading to adverse metabolic dysfunctions and diseases.
Description:
Alterations in physiological processes in pancreas have been associated with various metabolic dysfunctions and can result from environmental exposures, such as chemicals and diet. It was reported that environmental vinyl chloride (VC) exposure, a common industrial organochlorine and environmental pollutant, significantly exacerbated metabolic-related phenotypes in mice fed concurrently with high-fat diet (HFD) but not low-fat diet (LFD). However, little is known about the role of the pancreas in this interplay, especially at a proteomic level. The present study was undertaken to examine the protein responses to VC exposure in pancreas tissues of C57BL/6J mice fed LFD or HFD, with focus on the investigation of protein expression and/or phosphorylation levels of key protein biomarkers of carbohydrate, lipid, and energy metabolism, oxidative stress and detoxification, insulin secretion and regulation, cell growth, development, and communication, immunological responses and inflammation, and biomarkers of pancreatic diseases and cancers. We found that the protein alterations may indicate diet-mediated susceptibility in mouse pancreas induced by HFD to concurrent exposure of low levels of inhaled VC. These proteome biomarkers may lead to a better understanding of pancreas-mediated adaptive or adverse response and susceptibility to metabolic disease.
URLs/Downloads:
DOI: Vinyl chloride altered pancreas proteome and pathways associated with metabolism and predisposed mouse to enhanced metabolic stress
https://pubmed.ncbi.nlm.nih.gov/36892438/