Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

• Published in: PLoS biology Vol. 9; no. 6; p. e1000623
• Main Authors: Pietiläinen, Kirsi H., Róg, Tomasz, Seppänen-Laakso, Tuulikki, Virtue, Sam, Gopalacharyulu, Peddinti, Tang, Jing, Rodriguez-Cuenca, Sergio, Maciejewski, Arkadiusz, Naukkarinen, Jussi, Ruskeepää, Anna-Liisa, Niemelä, Perttu S., Yetukuri, Laxman, Tan, Chong Yew, Velagapudi, Vidya, Castillo, Sandra, Nygren, Heli, Hyötyläinen, Tuulia, Rissanen, Aila, Kaprio, Jaakko, Yki-Järvinen, Hannele, Vattulainen, Ilpo, Vidal-Puig, Antonio, Orešič, Matej
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2011; Public Library of Science (PLoS)
• Subjects: Acetyltransferases - metabolism; Adipocytes - metabolism; Adipocytes - pathology; Adipose tissue; Adipose Tissue - metabolism; Adult; Analysis; Biophysics/Theory and Simulation; Cell Biology/Membranes and Sorting; Cell Differentiation; Cell Membrane - metabolism; Cell membranes; Complications and side effects; Computational Biology/Metabolic Networks; Computational Biology/Molecular Dynamics; Computational Biology/Systems Biology; Development and progression; Diabetes and Endocrinology/Obesity; Diseases; Energy balance; Fat cells; Fats; Fatty Acid Elongases; Fatty acids; Fatty Acids, Unsaturated - metabolism; Female; Genetics; Humans; Inflammation; Insulin resistance; Lipid Metabolism; Lipids; Male; Membrane Fluidity; Metabolic disorders; Models, Biological; Molecular Dynamics Simulation; Obesity; Obesity - metabolism; Obesity - pathology; Pancreas; Phospholipids - metabolism; Physiological aspects; Physiology; Polyunsaturated fatty acids; Twin Studies as Topic; Young Adult; Europe; Cell Membrane; Obesity; Humans; Lipid Metabolism; Male; Phospholipids; Adipocytes; Membrane Fluidity; Molecular Dynamics Simulation; Young Adult; Fatty Acids, Unsaturated; Models, Biological; Adult; Female; Twin Studies as Topic; Cell Differentiation; Adipose Tissue; Acetyltransferases
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1000623

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.