Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans

K. H. Pietiläinen, T. Róg, Tuulikki Seppänen-Laakso, S. Virtue, Peddinti Gopalacharyulu, Jing Tang, S. Rodriguez-Cuenca, A. Maciejewski, J. Naukkarinen, Anna-Liisa Ruskeepää, Perttu Niemelä, Laxman Yetukuri, C. Y. Tan, Vidya Velagapudi, Sandra Castillo, Heli Nygren, Tuulia Hyötyläinen, A. Rissanen, J. Kaprio, H. Yki-JärvinenI. Vattulainen, A. Vidal-Puig, Matej Orešič

    Research output: Contribution to journalArticleScientificpeer-review

    155 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Article numbere1000623
    Number of pages14
    JournalPLoS Biology
    Volume9
    Issue number6
    DOIs
    Publication statusPublished - 2011
    MoE publication typeA1 Journal article-refereed

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