title: Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans.
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.
authors.affiliation: Department of Medicine, Division of Internal Medicine, and Department of Psychiatry, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.forename: Tomasz
authors.initials: T
authors.lastname: Róg
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Seppänen-Laakso
authors.forename: Sam
authors.initials: S
authors.lastname: Virtue
authors.forename: Peddinti
authors.initials: P
authors.lastname: Gopalacharyulu
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Sergio
authors.initials: S
authors.lastname: Rodriguez-Cuenca
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Maciejewski
authors.forename: Jussi
authors.initials: J
authors.lastname: Naukkarinen
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Ruskeepää
authors.forename: Perttu S
authors.initials: PS
authors.lastname: Niemelä
authors.forename: Laxman
authors.initials: L
authors.lastname: Yetukuri
authors.forename: Chong Yew
authors.initials: CY
authors.lastname: Tan
authors.forename: Vidya
authors.initials: V
authors.lastname: Velagapudi
authors.forename: Sandra
authors.initials: S
authors.lastname: Castillo
authors.forename: Heli
authors.initials: H
authors.lastname: Nygren
authors.forename: Tuulia
authors.initials: T
authors.lastname: Hyötyläinen
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008560:Membrane Fluidity; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D010743:Phospholipids / Q000378:metabolism; D018433:Twin Studies as Topic; D055815:Young Adult
chemical_list: C000630955:ELOVL6 protein, human; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases