Obesity is a complex disorder where the genome interacts with diet and environmental
factors to ultimately influence body mass, composition and shape. Numerous studies have
investigated how bulk lipid metabolism of adipose tissue changes with obesity, and in
particular how the composition of triglycerides (TGs) changes with increased adipocyte
expansion. However, reflecting the analytical challenge posed by examining non-TG lipids in
extracts dominated by TGs, the glycerophospholipid (PL) composition of cell membranes has
been seldom investigated. PLs contribute to a variety of cellular processes including
maintaining organelle functionality, providing an optimised environment for
membrane-associated proteins and as pools for metabolites (e.g. choline for one-carbon
metabolism and for methylation of DNA). We have conducted a comprehensive lipidomic
study of white adipose tissue in mice who become obese either through genetic modification
(ob/ob), diet (high fat diet) or a combination of the two using both solid phase extraction and
ion mobility to increase coverage of the lipidome. Composition changes in seven classes of
lipid (free fatty acids, diglycerides, TGs, phosphatidylcholines, lyso-phosphatidylcholines,
phosphatidylethanolamines, and phosphatidylserines) correlated with perturbations in
one-carbon metabolism and transcriptional changes in adipose tissue. We demonstrate that
changes in TGs that dominate the overall lipid composition of white adipose tissue are
distinct from diet-induced alterations of PLs, the predominant components of the cell
membranes. PLs correlate better with transcriptional and one-carbon metabolism changes
within the cell, suggesting the compositional changes that occur in cell membranes during
adipocyte expansion have far-reaching functional consequences. Data is available at
MetaboLights under the submission number: MTBLS1775
