Comprehensive Lipidome and Proteome Analyses to Identify the Inflammatory and Cardiometabolic Fingerprints of Metabolically “Healthy” Versus “Unhealthy” Obese Subjects

Abstract

Study ObjectiveObesity‐related co‐morbidities pose a serious health care system burden. However, 30% of obese subjects do not present with cardiometabolic complications. Here we perform comprehensive lipidome and proteome analyses to identify inflammatory and cardiometabolic fingerprints that characterize metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) phenotypes.MethodsObese patients (BMI 35–50) donated plasma before undergoing bariatric surgery (clinicaltrial.gov NCT02322073). Patients were classified as MHO (n=5) versus MUO (n=9) according to International Diabetes Federation criteria. Metabolically healthy lean (MHL, n=14) subjects were age‐ and sex‐matched to the obese cohort. Plasma samples were analyzed for 480 protein biomarkers related to inflammation and cardiometabolic processes in a multiplexed array. Samples were also subjected to untargeted lipidomics and targeted oxylipin lipidomics analyses.ResultsGene‐ontology term analysis of the 15 proteins that were significantly decreased/elevated in MHO vs. MUO patients revealed differences in inflammation, metabolism, apoptosis and fibrosis signaling pathways. Furthermore, lipidomics show distinct differences in the lipid profile of MHO and MUO groups. The MUO group displayed increased levels of ceramides, which are implicated in development of insulin resistance and cardiovascular diseases. In contrast, the MHO group exhibited increased levels of anandamide and dihomo‐gamma‐linolenoyl ethanolamide, which are lipids associated with anti‐inflammatory effects. The MUO group also exhibited elevated levels of the cardiometabolic risk factor plasminogen activator inhibitor 1 (PAI‐1). Interestingly, MHO patients presented with increased levels of myeloblastin, which is a serine protease that degrades the PAI‐1–stabilizing protein vitronectin.ConclusionIn conclusion, we have performed a comprehensive lipidomic and proteomic fingerprinting of MHO and MUO subjects. Our analyses reveal clear stratification of the groups and identify lipid mediators that may be of possible therapeutic use as novel interventions for obesity‐associated pathophysiologies. Work is ongoing to explore the molecular mechanism by which the identified proteins and lipid mediators affect cardiometabolic health in obese patients.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.