Integrative Lipidomics and Metabolomics for System-Level Understanding of the Metabolic Syndrome in Long-Term Treated HIV-Infected Individuals.
Sofie Olund Villumsen, Rui Benfeitas, Andreas Dehlbæk Knudsen, Marco Gelpi, Julie Høgh, Magda Teresa Thomsen, Daniel Murray, Henrik Ullum, Ujjwal Neogi, Susanne Dam Nielsen
Author Information
Sofie Olund Villumsen: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Rui Benfeitas: National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Andreas Dehlbæk Knudsen: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Marco Gelpi: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Julie Høgh: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Magda Teresa Thomsen: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Daniel Murray: Personalized Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE), Rigshospitalet, Copenhagen, Denmark.
Henrik Ullum: Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.
Ujjwal Neogi: The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm, Sweden.
Susanne Dam Nielsen: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
People living with HIV (PLWH) require life-long anti-retroviral treatment and often present with comorbidities such as metabolic syndrome (MetS). Systematic lipidomic characterization and its association with the metabolism are currently missing. We included 100 PLWH with MetS and 100 without MetS from the Copenhagen Comorbidity in HIV Infection (COCOMO) cohort to examine whether and how lipidome profiles are associated with MetS in PLWH. We combined several standard biostatistical, machine learning, and network analysis techniques to investigate the lipidome systematically and comprehensively and its association with clinical parameters. Additionally, we generated weighted lipid-metabolite networks to understand the relationship between lipidomic profiles with those metabolites associated with MetS in PLWH. The lipidomic dataset consisted of 917 lipid species including 602 glycerolipids, 228 glycerophospholipids, 61 sphingolipids, and 26 steroids. With a consensus approach using four different statistical and machine learning methods, we observed 13 differentially abundant lipids between PLWH without MetS and PLWH with MetS, which mainly belongs to diacylglyceride (DAG, n = 2) and triacylglyceride (TAG, n = 11). The comprehensive network integration of the lipidomics and metabolomics data suggested interactions between specific glycerolipids' structural composition patterns and key metabolites involved in glutamate metabolism. Further integration of the clinical data with metabolomics and lipidomics resulted in the association of visceral adipose tissue (VAT) and exposure to earlier generations of antiretroviral therapy (ART). Our integrative omics data indicated disruption of glutamate and fatty acid metabolism, suggesting their involvement in the pathogenesis of PLWH with MetS. Alterations in the lipid homeostasis and glutaminolysis need clinical interventions to prevent accelerated aging in PLWH with MetS.
