Characterization of depot-specific adipokine release in diet-induced obese mice reveals a distinct secretion profile in paracardial adipose tissue

Obesity is characterized by excessive adipose tissue deposition across multiple depots, accompanied by profound alterations in systemic metabolism. Beyond their role in lipid storage, adipose tissues are active endocrine organs that secrete a range of bioactive proteins, i.e., adipokines, that regulate energy homeostasis, inflammation, and metabolic health. Alterations in adipokine secretion are increasingly recognized as key contributors to the development of obesity-related comorbidities. Here, we investigate depot-specific patterns of adipokine release from paracardial (PAT), inguinal (ING), and epididymal (EPI) adipose tissues in healthy lean mice and mice fed a high-fat diet. Using untargeted proteomics, we identify distinct secretory profiles across depots, revealing marked heterogeneity in the composition and magnitude of secreted proteins. In healthy lean mice, PAT exhibited the highest overall protein secretion rates, with enrichment in proteins linked to cellular and oxidative stress responses. High fat feeding induced extensive remodelling of the adipose secretome across all depots. EPI adipose tissue displayed increased secretion of proteins involved in cellular stress, injury and inflammation, whereas both ING and PAT depots demonstrated substantial suppression of protein release, including reductions in proteins associated with carbohydrate homeostasis and insulin signalling. These findings highlight that obesity drives depot-specific adaptations in adipokine secretion, potentially contributing to regional differences in metabolic risk. Together, this study provides an in-depth proteomic characterization of adipose tissue secretory remodeling in diet-induced obesity, offering new insights into how distinct fat depots influence systemic metabolic regulation.