Abstract
| Original language | English |
|---|---|
| Article number | e1000623 |
| Number of pages | 14 |
| Journal | PLoS Biology |
| Volume | 9 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2011 |
| MoE publication type | A1 Journal article-refereed |
Fingerprint
Cite this
}
Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans. / Pietiläinen, K. H.; Róg, T.; Seppänen-Laakso, Tuulikki; Virtue, S.; Gopalacharyulu, Peddinti; Tang, Jing; Rodriguez-Cuenca, S.; Maciejewski, A.; Naukkarinen, J.; Ruskeepää, Anna-Liisa; Niemelä, Perttu; Yetukuri, Laxman; Tan, C. Y.; Velagapudi, Vidya; Castillo, Sandra; Nygren, Heli; Hyötyläinen, Tuulia; Rissanen, A.; Kaprio, J.; Yki-Järvinen, H.; Vattulainen, I.; Vidal-Puig, A.; Orešič, Matej (Corresponding Author).
In: PLoS Biology, Vol. 9, No. 6, e1000623, 2011.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans
AU - Pietiläinen, K. H.
AU - Róg, T.
AU - Seppänen-Laakso, Tuulikki
AU - Virtue, S.
AU - Gopalacharyulu, Peddinti
AU - Tang, Jing
AU - Rodriguez-Cuenca, S.
AU - Maciejewski, A.
AU - Naukkarinen, J.
AU - Ruskeepää, Anna-Liisa
AU - Niemelä, Perttu
AU - Yetukuri, Laxman
AU - Tan, C. Y.
AU - Velagapudi, Vidya
AU - Castillo, Sandra
AU - Nygren, Heli
AU - Hyötyläinen, Tuulia
AU - Rissanen, A.
AU - Kaprio, J.
AU - Yki-Järvinen, H.
AU - Vattulainen, I.
AU - Vidal-Puig, A.
AU - Orešič, Matej
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pbio.1000623
DO - 10.1371/journal.pbio.1000623
M3 - Article
VL - 9
JO - PLoS Biology
JF - PLoS Biology
SN - 1544-9173
IS - 6
M1 - e1000623
ER -