Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)

Deposition and mobilization of fat in an organism are tightly controlled by multiple levels of endocrine and neuroendocrine regulation. Because these hormonal mechanisms ultimately act by affecting biochemical reactions of fat synthesis or utilization, obesity could be also modulated by altering dir...

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Autores principales: Singh, Sharda P., Niemczyk, Maciej, Zimniak, Ludwika, Zimniak, Piotr
Formato: Texto
Lenguaje:English
Publicado: Impact Journals LLC 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815766/
https://www.ncbi.nlm.nih.gov/pubmed/20157589
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author Singh, Sharda P.
Niemczyk, Maciej
Zimniak, Ludwika
Zimniak, Piotr
author_facet Singh, Sharda P.
Niemczyk, Maciej
Zimniak, Ludwika
Zimniak, Piotr
author_sort Singh, Sharda P.
collection PubMed
description Deposition and mobilization of fat in an organism are tightly controlled by multiple levels of endocrine and neuroendocrine regulation. Because these hormonal mechanisms ultimately act by affecting biochemical reactions of fat synthesis or utilization, obesity could be also modulated by altering directly the underlying lipid biochemistry. We have previously shown that genetically modified mice with an elevated level of the lipid peroxidation product 4-HNE become obese. We now demonstrate that the process is phylogenetically conserved and thus likely to be universal. In the nematode C. elegans, disruption of either conjugation or oxidation of 4-HNE leads to fat accumulation, whereas augmentation of 4-HNE conjugation results in a lean phenotype. Moreover, direct treatment of C. elegans with synthetic 4-HNE causes increased lipid storage, directly demonstrating a causative role of 4-HNE. The postulated mechanism, which involves modulation of acetyl-CoA carboxylase activity, could contribute to the triggering and maintenance of the obese phenotype on a purely metabolic level.
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spelling pubmed-28157662010-02-12 Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE) Singh, Sharda P. Niemczyk, Maciej Zimniak, Ludwika Zimniak, Piotr Aging (Albany NY) Research Article Deposition and mobilization of fat in an organism are tightly controlled by multiple levels of endocrine and neuroendocrine regulation. Because these hormonal mechanisms ultimately act by affecting biochemical reactions of fat synthesis or utilization, obesity could be also modulated by altering directly the underlying lipid biochemistry. We have previously shown that genetically modified mice with an elevated level of the lipid peroxidation product 4-HNE become obese. We now demonstrate that the process is phylogenetically conserved and thus likely to be universal. In the nematode C. elegans, disruption of either conjugation or oxidation of 4-HNE leads to fat accumulation, whereas augmentation of 4-HNE conjugation results in a lean phenotype. Moreover, direct treatment of C. elegans with synthetic 4-HNE causes increased lipid storage, directly demonstrating a causative role of 4-HNE. The postulated mechanism, which involves modulation of acetyl-CoA carboxylase activity, could contribute to the triggering and maintenance of the obese phenotype on a purely metabolic level. Impact Journals LLC 2008-12-18 /pmc/articles/PMC2815766/ /pubmed/20157589 Text en Copyright: ©2009 Singh et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Singh, Sharda P.
Niemczyk, Maciej
Zimniak, Ludwika
Zimniak, Piotr
Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)
title Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)
title_full Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)
title_fullStr Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)
title_full_unstemmed Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)
title_short Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)
title_sort fat accumulation in caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-hydroxynonenal (4-hne)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815766/
https://www.ncbi.nlm.nih.gov/pubmed/20157589
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