Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent

Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. Chronic exposure to MeHg in human populations shows an association with diabetes mellitus and metabolic syndrome (MS). As the incidences of both obesity and MS are on the ris...

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Autores principales:	Nicole Crawford, Megan Martell, Tyson Nielsen, Belal Khalil, Farooq Imtiaz, Etienne Nguidjo, Jennifer L. Newell-Caito, Julia Bornhorst, Tanja Schwerdtle, Samuel W. Caito
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	methylmercury diet cholesterol high fat low fat Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/dedb094b658041e3a0e9d01f44b74e8e
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spelling	oai:doaj.org-article:dedb094b658041e3a0e9d01f44b74e8e2021-11-25T19:08:06ZMethylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent10.3390/toxics91102872305-6304https://doaj.org/article/dedb094b658041e3a0e9d01f44b74e8e2021-11-01T00:00:00Zhttps://www.mdpi.com/2305-6304/9/11/287https://doaj.org/toc/2305-6304Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. Chronic exposure to MeHg in human populations shows an association with diabetes mellitus and metabolic syndrome (MS). As the incidences of both obesity and MS are on the rise globally, it is important to understand the potential role of MeHg in the development of the disease. There is a dearth of information on dietary interactions between MeHg and lipids, which play an important role in developing MS. We have previously shown that MeHg increases food seeking behaviors, lipid levels, fat storage, and pro-adipogenic gene expression in <i>C. elegans</i> fed the standard OP50 <i>Escherichia coli</i> diet. However, we hypothesized that these metabolic changes could be prevented if the worms were fed a bacterial diet lower in lipid content. We tested whether <i>C. elegans</i> developed metabolic alterations in response to MeHg if they were fed two alternative <i>E. coli</i> strains (HT115 and HB101) that are known absorb significantly less lipids from their media. Additionally, to explore the effect of a high-lipid and high-cholesterol diet on MeHg-induced metabolic dysfunction, we supplemented the OP50 strain with twice the standard concentration of cholesterol in the nematode growth media. Wild-type worms fed either the HB101 or HT115 diet were more resistant to MeHg than the worms fed the OP50 diet, showing a significant right-hand shift in the dose–response survival curve. Worms fed the OP50 diet supplemented with cholesterol were more sensitive to MeHg, showing a significant left-hand shift in the dose–response survival curve. Changes in sensitivity to MeHg by differential diet were not due to altered MeHg intake in the worms as measured by inductively coupled mass spectrometry. Worms fed the low-fat diets showed protection from MeHg-induced metabolic changes, including decreased food consumption, lower triglyceride content, and lower fat storage than the worms fed either of the higher-fat diets. Oxidative stress is a common characteristic of both MeHg exposure and high-fat diets. Worms fed either OP50 or OP50 supplemented with cholesterol and treated with MeHg had significantly higher levels of reactive oxygen species, carbonylated proteins, and loss of glutathione than the worms fed the HT115 or HB101 low-lipid diets. Taken together, our data suggest a synergistic effect of MeHg and dietary lipid levels on MeHg toxicity and fat metabolism in <i>C. elegans</i>, which may affect the ability of MeHg to cause metabolic dysfunction.Nicole CrawfordMegan MartellTyson NielsenBelal KhalilFarooq ImtiazEtienne NguidjoJennifer L. Newell-CaitoJulia BornhorstTanja SchwerdtleSamuel W. CaitoMDPI AGarticlemethylmercurydietcholesterolhigh fatlow fatChemical technologyTP1-1185ENToxics, Vol 9, Iss 287, p 287 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	methylmercury diet cholesterol high fat low fat Chemical technology TP1-1185
spellingShingle	methylmercury diet cholesterol high fat low fat Chemical technology TP1-1185 Nicole Crawford Megan Martell Tyson Nielsen Belal Khalil Farooq Imtiaz Etienne Nguidjo Jennifer L. Newell-Caito Julia Bornhorst Tanja Schwerdtle Samuel W. Caito Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent
description	Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. Chronic exposure to MeHg in human populations shows an association with diabetes mellitus and metabolic syndrome (MS). As the incidences of both obesity and MS are on the rise globally, it is important to understand the potential role of MeHg in the development of the disease. There is a dearth of information on dietary interactions between MeHg and lipids, which play an important role in developing MS. We have previously shown that MeHg increases food seeking behaviors, lipid levels, fat storage, and pro-adipogenic gene expression in <i>C. elegans</i> fed the standard OP50 <i>Escherichia coli</i> diet. However, we hypothesized that these metabolic changes could be prevented if the worms were fed a bacterial diet lower in lipid content. We tested whether <i>C. elegans</i> developed metabolic alterations in response to MeHg if they were fed two alternative <i>E. coli</i> strains (HT115 and HB101) that are known absorb significantly less lipids from their media. Additionally, to explore the effect of a high-lipid and high-cholesterol diet on MeHg-induced metabolic dysfunction, we supplemented the OP50 strain with twice the standard concentration of cholesterol in the nematode growth media. Wild-type worms fed either the HB101 or HT115 diet were more resistant to MeHg than the worms fed the OP50 diet, showing a significant right-hand shift in the dose–response survival curve. Worms fed the OP50 diet supplemented with cholesterol were more sensitive to MeHg, showing a significant left-hand shift in the dose–response survival curve. Changes in sensitivity to MeHg by differential diet were not due to altered MeHg intake in the worms as measured by inductively coupled mass spectrometry. Worms fed the low-fat diets showed protection from MeHg-induced metabolic changes, including decreased food consumption, lower triglyceride content, and lower fat storage than the worms fed either of the higher-fat diets. Oxidative stress is a common characteristic of both MeHg exposure and high-fat diets. Worms fed either OP50 or OP50 supplemented with cholesterol and treated with MeHg had significantly higher levels of reactive oxygen species, carbonylated proteins, and loss of glutathione than the worms fed the HT115 or HB101 low-lipid diets. Taken together, our data suggest a synergistic effect of MeHg and dietary lipid levels on MeHg toxicity and fat metabolism in <i>C. elegans</i>, which may affect the ability of MeHg to cause metabolic dysfunction.
format	article
author	Nicole Crawford Megan Martell Tyson Nielsen Belal Khalil Farooq Imtiaz Etienne Nguidjo Jennifer L. Newell-Caito Julia Bornhorst Tanja Schwerdtle Samuel W. Caito
author_facet	Nicole Crawford Megan Martell Tyson Nielsen Belal Khalil Farooq Imtiaz Etienne Nguidjo Jennifer L. Newell-Caito Julia Bornhorst Tanja Schwerdtle Samuel W. Caito
author_sort	Nicole Crawford
title	Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent
title_short	Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent
title_full	Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent
title_fullStr	Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent
title_full_unstemmed	Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent
title_sort	methylmercury-induced metabolic alterations in <i>caenorhabditis elegans</i> are diet-dependent
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dedb094b658041e3a0e9d01f44b74e8e
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Methylmercury-Induced Metabolic Alterations in <i>Caenorhabditis elegans</i> Are Diet-Dependent

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