Metabolic heterogeneity in adipose resident immunocytes and its link to type 2 diabetes via response to catabolism defects

作者：Shanshan Huang, Xuetao Chen, Yue Yuan, Yuan Yuan, Lei Shen, Hongdong Wang, Wenjuan Tang, Yan Bi, Tianyu Wu · 发表于：Genomics · 年份：2025 · DOI：10.1016/j.ygeno.2025.111152 · 被引用次数：1 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Immune cells in cancer、Gut microbiota and health

Adipose resident immune cells are vital contributors to adipose dysfunction in metabolic diseases. While current research has focused on immunogenic heterogeneities, investigations into metabolic heterogeneity are needed to reveal the diverse responses to metabolic perturbations. This study dissected and profiled the metabolic activities of 9243 resident immunocytes from visceral adipose tissue. Clustering analysis revealed seven metabolic patterns with diverse functions. Differential analysis showed that these metabolic patterns exhibit heterogeneous responses to systemic metabolic reductions paralleling a type 2 diabetes-associated trajectory. Graph theory analysis of correlation networks further delineated that impaired capacities to catabolize complex lipids with peroxisomes and degrade amino acids are core metabolic defects regulating resident immune cell functions in type 2 diabetes. Collectively, these results unveiled the role of metabolic heterogeneity in the diverse responses of resident immunocytes to metabolic perturbations, with lipid and amino acid catabolic defects as core metabolic factors contributing to type 2 diabetes. • Metabolic heterogeneity shapes functional diversity of adipose resident immunocytes. • Metabolic rewiring correlates with altered cellular signalling in metabolic diseases. • T2D presents a path featuring metabolic decline preceding immune dysfunction. • Impaired peroxisomal and amino acid catabolism links metabolism to immune dysfunction i...