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Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans
Department of Medicine, Division of Internal Medicine, Department of Psychiatry, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland; Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine Finland, Helsinki, Finland.
Department of Physics, Tampere University of Technology, Tampere, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
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2011 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 9, no 6, e1000623Article in journal (Refereed) Published
Abstract [en]

Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved states of obesity by investigating a separated set of individuals considered to be morbidly obese. Despite lower dietary polyunsaturated fatty acid intake, the obese twin individuals had increased proportions of palmitoleic and arachidonic acids in their adipose tissue, including increased levels of ethanolamine plasmalogens containing arachidonic acid. Information gathered from these experimental groups was used for molecular dynamics simulations of lipid bilayers combined with dependency network analysis of combined clinical, lipidomics, and gene expression data. The simulations suggested that the observed lipid remodeling maintains the biophysical properties of lipid membranes, at the price, however, of increasing their vulnerability to inflammation. Conversely, in morbidly obese subjects, the proportion of plasmalogens containing arachidonic acid in the adipose tissue was markedly decreased. We also show by in vitro Elovl6 knockdown that the lipid network regulating the observed remodeling may be amenable to genetic modulation. Together, our novel approach suggests a physiological mechanism by which adaptation of adipocyte membranes to adipose tissue expansion associates with positive energy balance, potentially leading to higher vulnerability to inflammation in acquired obesity. Further studies will be needed to determine the cause of this effect.

Place, publisher, year, edition, pages
Public Library of Science , 2011. Vol. 9, no 6, e1000623
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-59354DOI: 10.1371/journal.pbio.1000623ISI: 000292191200002PubMedID: 21666801Scopus ID: 2-s2.0-79959791037OAI: oai:DiVA.org:oru-59354DiVA: diva2:1135879
Note

Funding Agencies:

EU  

HEPADIP  

Academy of Finland  

Helsinki University Central Hospital  

Jalmari and Rauha Ahokas  

Yrjo Jahnsson  

Biomedicum Helsinki  

Novo Nordisk Foundations  

BBSRC 

Available from: 2017-08-24 Created: 2017-08-24 Last updated: 2017-09-04Bibliographically approved

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