Biology subjects

Thomsen, H. H.

Publications and source records attributed to Thomsen, H. H..

3 recordsLinked to original sources

bioRxiv2026

Dynamic Responses to an Inflammatory Challenge Distinguish Metabolic Health Across Lean and Obese Individuals

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.

immunology↗

bioRxiv2026

Sex-specific remodeling of the human adipose tissue vascular niche in obesity

AO_SCPLOWBSTRACTC_SCPLOWObesity remodels the subcutaneous adipose tissue (SAT) vasculature and contributes to cardiometabolic risk, yet potential sex differences in this process remain poorly defined. Here, we integrated single-nucleus transcriptomics and histological analyses of human SAT to reveal pronounced sexual dimorphism within the vascular niche. Obese males exhibit mural cell loss, increased collagen deposition, and inflammatory endothelial activation, including enhanced antigen presentation programs. In contrast, females display preserved mural coverage and increased lipid-handling and redox-adaptive pathways. These coordinated structural and transcriptional differences position the adipose endothelium as a sex-divergent regulator of obesity-associated cardiometabolic vulnerability.

cell biology↗

bioRxiv2024

Defining the Vascular Niche of Human Adipose Tissue Across Metabolic Conditions

IntroductionAdipose tissue homeostasis depends on a healthy vascular network. Vascular malfunction is a hallmark of obesity1, and vascular endothelial dysfunction, in particular, accelerates metabolic diseases, including obesity and diabetes. Single-cell transcriptomics studies have mapped the cellular landscape of human white adipose tissue (WAT)2-8. However, the vascular niche remains relatively undefined9, especially regarding its heterogeneity, function, and role in metabolic disease. To address this gap, we created a single-cell transcriptome atlas of human subcutaneous adipose tissue (SAT), comprising nearly 70,000 vascular cells from 65 individuals. We characterized seven canonical adipose tissue endothelial cell (AdEC) subtypes and identified a distinct heterogenous population, here referred to as sub-AdECs. Sub-AdECs exhibit gene signatures characteristic of multiple cell types, including mesenchymal, adipocytic, and immune, suggesting they possess diverse properties and identities. Through computational analyses and whole-mount imaging, we validated the occurrence of sub-AdECs and show that these cells likely arise through endothelial-mesenchymal transition (EndMT), the modulation of which limits obesity-associated adipose tissue inflammation and fibrosis. Furthermore, we compared the transcriptomes of vascular cells from individuals living with or without obesity and type 2 diabetes and find metabolic disease-associated inflammatory and fibrotic transcriptomic patterns. The atlas and accompanying analyses establish a solid foundation for investigations into the biology of the adipose tissue vascular niche and its contribution to the pathogenesis of metabolic disease.

cell biology↗