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Title: Methylmercury Induces Metabolic Alterations in Caenorhabditis elegans: Role for C/EBP Transcription Factor.

Authors: Caito, Samuel W; Newell-Caito, Jennifer; Martell, Megan; Crawford, Nicole; Aschner, Michael

Published In Toxicol Sci, (2020 03 01)

Abstract: Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. We have previously shown that MeHg causes metabolic alterations in Caenorhabditis elegans, leading to decreased nicotinamide adenine dinucleotide cofactor, mitochondrial dysfunction, and oxidative stress. We were, therefore, interested in whether MeHg also affects nutrient metabolism, particularly lipid homeostasis, which may contribute to the development of metabolic conditions such as obesity or metabolic syndrome (MS). RNA from wild-type worms exposed to MeHg was collected immediately after treatment and used for gene expression analysis by DNA microarray. MeHg differentially regulated 215 genes, 17 genes involved in lipid homeostasis, and 12 genes involved in carbohydrate homeostasis. Of particular interest was cebp-1, the worm ortholog to human C/EBP, a pro-adipogenic transcription factor implicated in MS. MeHg increased the expression of cebp-1 as well as pro-adipogenic transcription factors sbp-1 and nhr-49, triglyceride synthesis enzyme acl-6, and lipid transport proteins vit-2 and vit-6. Concurrent with the altered gene expression, MeHg increased triglyceride levels, lipid storage, and feeding behaviors. Worms expressing mutant cebp-1 were protected from MeHg-induced alterations in lipid content, feeding behaviors, and gene expression, highlighting the importance of this transcription factor in the worm's response to MeHg. Taken together, our data demonstrate that MeHg induces biochemical, metabolic, and behavioral changes in C. elegans that can lead to metabolic dysfunction.

PubMed ID: 31851340 Exiting the NIEHS site

MeSH Terms: Adipogenesis/drug effects; Adipogenesis/genetics; Animals; Animals, Genetically Modified; CCAAT-Enhancer-Binding Proteins/genetics; CCAAT-Enhancer-Binding Proteins/metabolism*; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism*; Caenorhabditis elegans/drug effects*; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Energy Metabolism/drug effects*; Energy Metabolism/genetics; Feeding Behavior/drug effects; Gene Expression Regulation; Lipid Metabolism/drug effects*; Lipid Metabolism/genetics; Locomotion/drug effects; Methylmercury Compounds/toxicity*; Mutation

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Last Reviewed: October 07, 2024