Dynamic Responses to an Inflammatory Challenge Distinguish Metabolic Health Across Lean and Obese Individuals
Year: 2026
Type: preprint
Abstract: Inflammation is a key driver of cardiometabolic disease, yet it remains unclear whether systemic inflammatory markers can distinguish metabolically healthy from unhealthy individuals or capture the temporal dynamics of inflammation. Here, we combined systemic immune profiling with a cantharidin-induced peripheral blister model to investigate dynamic inflammatory regulation across metabolic phenotypes in metabolically healthy lean (MHL), metabolically unhealthy lean (MUL), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) individuals. While systemic inflammation was elevated in obesity, differences between metabolically healthy and unhealthy groups were modest, with limited discrimination by plasma proteomics, circulating leukocyte phenotyping, and whole-blood transcriptomics. In contrast, the dynamic response to inflammatory challenge revealed pronounced differences at proteomic, cellular, and transcriptomic levels. Metabolically unhealthy individuals exhibited exaggerated early innate immune responses, impaired inflammatory resolution and tissue repair, reduced recruitment of reparative immune cells, and sustained T cell presence. Transcriptomic analyses further showed blunted dynamic gene regulation and defective epidermal barrier restoration. These findings indicate that metabolic health is better reflected in tissue-level inflammatory dynamics than in systemic measures.
Authors: Saeideh Tavajoh, Bianca E. Suur, Madison Clark, Adriana A. Becerril-Campos, Elia Velasco, Brigita Medelytė, Line Boel Nørregaard, Stine Julie Tingskov, Amanda Bæk, Lykke Skaarup, Erik Schrøder, Maryam Dost, Sigrid Bjerge Gribsholt, Jens M. Bruun, Marianne Quiding Järbrink, Sofia Nyström, Ida Bergström, Catherine Åhlund, Jane Palsgaard Pedersen, Niels Jessen, Lin Lin, Andras Harazin, Henrik H. Thomsen, Per-Anders Jansson, Robert Blomgran, Stephan Lange, Matúš Soták, Emma Börgeson
Institutions: Aarhus University, Aarhus University Hospital, Steno Diabetes Center Aarhus, Sahlgrenska University Hospital, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Regional Hospital Central Jutland, Linköping University, Region Östergötland, University of California San Diego
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G109333521, G2405018015, The role of obscurin and Obsl1 as key determinants for diastolic function, The circular car, G4653588445, Signaling Pathways in Dilated Cardiomyopathy, G6248030105, G694232863, A precision medicine approach to harness the therapeutic potential of lipoxins to reduce inflammation and obesity-related cardiometabolic disease
OpenAlex ID: W7213558428