Multi-omics Integrative Investigation of Fatty Acid Metabolism in Obese and Lean Subcutaneous Tissue

White adipose tissue (WAT) plays a central role in whole-body energy homeostasis through storage and release of fatty acids. A deeper understanding of the complex and highly integrated pathways regulating WAT fatty acid metabolism, and how they are altered with obesity, is necessary for diagnostic and therapeutic innovations in nutritional disorders. In this multi-omics study, we investigated the influence of obesity on fatty acid metabolism in human subcutaneous adipose tissue (SAT) using an approach that integrated transcriptomic, peptidomic, and fatty acid analyses. Notably, all analyses were conducted in the same adipose tissue sample from each participant, thus minimizing the chance of spurious results. In a sample of SAT from the periumbilical abdominal region of obese (n = 11, mean body mass index [BMI] = 35.0 ± 1.2 kg/m²) and lean subjects (n = 9, mean BMI = 22.1 ± 0.5 kg/m²), we found that obese SAT tended to have higher relative amounts of specific monounsaturated fatty acids and n-6 polyunsaturated fatty acids, and lower amounts of saturated fatty acids (p < 0.05). These changes were associated with differential regulation of lipogenic and lipolytic pathways in obese SAT. Fatty acid analysis showed changes in estimated fatty acid desaturase and elongase activities between lean and obese SAT (p < 0.05). Biomarkers of lipogenesis (e.g., fatty acid synthase protein) were differentially regulated between lean and obese SAT. These changes were noted in conjunction with increases in extracellular matrix remodeling proteins. Transcriptomic data revealed that the key regulators of lipolysis were reduced in obese SAT. This integrative multi-omics analysis collectively shows that obese SAT has a distinct fatty acid signature compared to lean SAT and the pathways underlying fatty acid metabolism are broadly regulated at the level of gene expression and protein abundance.