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AdipoAtlas: A Reference Lipidome for Human White Adipose Tissue

ABSTRACT: Obesity, characterized by expansion and metabolic dysregulation of white adipose tissue (WAT), has reached pandemic proportions and acts as a primer for a wide range of metabolic disorders. Remodelling of WAT lipidome in obesity and associated comorbidities can explain disease etiology and provide valuable diagnostic and prognostic markers. To support understanding of WAT lipidome remodelling at molecular level, we performed in-depth lipidomics profiling of human subcutaneous and visceral WAT of lean and obese individuals. Tissue-tailored preanalytical and analytical workflows allowed accurate identification and semi-absolute quantification of 1636 and 737 lipid molecular species, respectively, and summarized here in a form of human WAT reference lipidome. Deep lipidomic profiling allowed to identify main lipid (sub)classes undergoing depot/phenotype specific remodelling. Furthermore, previously unanticipated diversity of WAT ceramides was uncovered. AdipoAtlas reference lipidome will serve as a data-rich resource for development of WAT-specific high-throughput methods and as a scaffold for systems medicine data integration.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Adipose Tissue

DISEASE(S): Obesity

SUBMITTER: Maria Fedorova

PROVIDER: ST001738 | MetabolomicsWorkbench | Mon Jan 11 00:00:00 GMT 2021

REPOSITORIES: MetabolomicsWorkbench

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Project description:Background: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. Fsp27 is expressed in both BAT and WAT and promotes lipid storage and the development of obesity and diabetes. In addition, Fsp27-deficient white adipocytes acquired certain BAT-like properties including reduced lipid droplet size and increased mitochondrial activity. Using microarray and semi-quantitative real-time PCR analyses, we systematically analyzed the gene expression profile in Fsp27-deficient WAT and BAT. Results: We observed that BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of Fsp27-/- mice. Expression levels of BAT-selective genes were also dramatically up-regulated in the WAT of leptin and Fsp27 double deficient mice. Furthermore, we observed that expression levels of genes in multiple metabolic pathways including oxidative phosphorylation, the TCA cycle and fatty acid synthesis and oxidation were increased in the Fsp27-/- WAT. In contrast, expression levels for extracellular matrix remodeling, the classic complement pathway and TGF-β signaling"were down-regulated in the WAT of Fsp27-/- mice. Most importantly, regulatory factors that determine BAT identity such as CEBPα/β, PRDM16 and major components in the cAMP pathway were markedly up-regulated in the WAT of Fsp27-/- mice. Interestingly, we observed distinct gene expression profiles in the BAT of Fsp27-/- mice. Conclusion: Our data suggest that Fsp27 acts at upstream to control gene expression of diverse pathways, in particular the expression of regulatory factors that determine the identity of BAT and WAT. Therefore, Fsp27 is an important molecular determinant for the identity of WAT, and loss of Fsp27 leads to the conversion of WAT to a BAT-like tissue. Total RNAs were extracted from individual gonadal WAT of five pairs of 3-month-old wild-type and Fsp27-null male mice. Equal amounts of RNA from five pairs of mice with each genotype were pooled to form RNA pools (total 45 μg). Duplicate experiments were carried out.

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AdipoAtlas: A Reference Lipidome for Human White Adipose Tissue

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