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Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice

BACKGROUND: The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes c...

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Detalles Bibliográficos
Autores principales: Mutch, David M, O'Maille, Grace, Wikoff, William R, Wiedmer, Therese, Sims, Peter J, Siuzdak, Gary
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868938/
https://www.ncbi.nlm.nih.gov/pubmed/17355638
http://dx.doi.org/10.1186/gb-2007-8-3-r38
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author Mutch, David M
O'Maille, Grace
Wikoff, William R
Wiedmer, Therese
Sims, Peter J
Siuzdak, Gary
author_facet Mutch, David M
O'Maille, Grace
Wikoff, William R
Wiedmer, Therese
Sims, Peter J
Siuzdak, Gary
author_sort Mutch, David M
collection PubMed
description BACKGROUND: The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes characteristic of metabolic syndrome. Because adipose tissue is increasingly recognized as an endocrine organ, capable of releasing small molecules that modulate disparate physiological processes, we examined the plasma from wild-type, Plscr1-/-, Plscr3-/- and Plscr1&3-/- mice. Using an untargeted comprehensive metabolite profiling approach coupled with targeted gene expression analyses, the perturbed biochemistry and functional redundancy of PLSCR proteins was assessed. RESULTS: Nineteen metabolites were differentially and similarly regulated in both Plscr3-/- and Plscr1&3-/- animals, of which five were characterized from accurate mass, tandem mass spectrometry data and their correlation to the Metlin database as lysophosphatidylcholine (LPC) species enriched with C16:1, C18:1, C20:3, C20:5 and C22:5 fatty acids. No significant changes in the plasma metabolome were detected upon elimination of PLSCR1, indicating that increases in pro-inflammatory lipids are specifically associated with the obese state of Plscr3-deficient animals. Correspondingly, increases in white adipose lipogenic gene expression confirm a role for PLSCR3 in adipose lipid metabolism. CONCLUSION: The untargeted profiling of circulating metabolites suggests no detectable functional redundancies between PLSCR proteins; however, this approach simultaneously identified previously unrecognized lipid metabolites that suggest a novel molecular link between obesity, inflammation and the downstream consequences associated with PLSCR3-deficiency.
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spelling pubmed-18689382007-05-16 Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice Mutch, David M O'Maille, Grace Wikoff, William R Wiedmer, Therese Sims, Peter J Siuzdak, Gary Genome Biol Research BACKGROUND: The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes characteristic of metabolic syndrome. Because adipose tissue is increasingly recognized as an endocrine organ, capable of releasing small molecules that modulate disparate physiological processes, we examined the plasma from wild-type, Plscr1-/-, Plscr3-/- and Plscr1&3-/- mice. Using an untargeted comprehensive metabolite profiling approach coupled with targeted gene expression analyses, the perturbed biochemistry and functional redundancy of PLSCR proteins was assessed. RESULTS: Nineteen metabolites were differentially and similarly regulated in both Plscr3-/- and Plscr1&3-/- animals, of which five were characterized from accurate mass, tandem mass spectrometry data and their correlation to the Metlin database as lysophosphatidylcholine (LPC) species enriched with C16:1, C18:1, C20:3, C20:5 and C22:5 fatty acids. No significant changes in the plasma metabolome were detected upon elimination of PLSCR1, indicating that increases in pro-inflammatory lipids are specifically associated with the obese state of Plscr3-deficient animals. Correspondingly, increases in white adipose lipogenic gene expression confirm a role for PLSCR3 in adipose lipid metabolism. CONCLUSION: The untargeted profiling of circulating metabolites suggests no detectable functional redundancies between PLSCR proteins; however, this approach simultaneously identified previously unrecognized lipid metabolites that suggest a novel molecular link between obesity, inflammation and the downstream consequences associated with PLSCR3-deficiency. BioMed Central 2007 2007-03-13 /pmc/articles/PMC1868938/ /pubmed/17355638 http://dx.doi.org/10.1186/gb-2007-8-3-r38 Text en Copyright ©2007 Mutch et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Mutch, David M
O'Maille, Grace
Wikoff, William R
Wiedmer, Therese
Sims, Peter J
Siuzdak, Gary
Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
title Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
title_full Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
title_fullStr Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
title_full_unstemmed Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
title_short Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
title_sort mobilization of pro-inflammatory lipids in obese plscr3-deficient mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868938/
https://www.ncbi.nlm.nih.gov/pubmed/17355638
http://dx.doi.org/10.1186/gb-2007-8-3-r38
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