Transcriptomic and Metabolomic Analyses Reveal Distinctive Metabolic Characteristics of Superficial and Deep Subcutaneous Adipose Tissues

Background: The purpose of the study was to find out the molecular and metabolic characteristics of human superficial (SSAT) and deep subcutaneous adipose tissue (DSAT) by performing transcriptomics and metabolomics analysis Methods: We conducted RNA-sequencing and metabolome analysis of SSAT and DSAT in a 48-year-old female patient with a BMI of 27.6 kg/m2. Six samples for each group were collected during a deep inferior epigastric perforator flap breast reconstruction. The calculated transcripts per million values were processed for unsupervised hierarchically clustered heat map generation, and Gene set enrichment analysis. For metabolomics analysis, the samples were analyzed in two modes for cationic and anionic metabolites by Capillary Electrophoresis Time-of-Flight Mass Spectrometry (CE-TOFMS). The metabolome was processed for principal component analysis (PCA) and heat map generation. For indirect metabolic flux analyses, primary adipocytes obtained from SSAT and DSAT were analyzed with Seahorse® extracellular flux analyzer. Results: PCA and heat map data revealed global differences in the transcriptome and metabolome of SSAT and DSAT. The top up-regulated gene sets in the SSAT were related to adipogenesis (FDR q < 0.0001), oxidative phosphorylation (FDR q < 0.0001), fatty acid metabolism (FDR q < 0.0001) and glycolysis (FDR q = 0.001), while inflammatory response (FDR q < 0.05) was the top up-regulated gene set in DSAT. Consequently, the metabolites related to glycolysis were abundant in SSAT, while the metabolites related to fatty acid metabolism and oxidative phosphorylation were abundant in DSAT. In cellular flux analysis, SSAT showed higher level of glycolysis and spare oxidative phosphorylation capacities. Conclusion: The global transcriptome and metabolome difference suggest that human superficial and deep subcutaneous adipose tissue are metabolically distinguishable subcompartments.