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

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 9,243 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.