Anatomical Atlas of Kinase Responsiveness to Weight Gain: Adipose Depot Reprogramming in Diet-Induced Adiposity

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood. Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The kinases most significantly altered across adipose tissue depots were identified, revealing depot-specific combinations of hyperactive and hypoactive kinase pathways involved in adiposity. Results: Our findings demonstrate distinct kinase families that regulate specific fat depots, with potential implications for drug discovery and therapeutic resistance. Conclusions: This research presents a comprehensive adipokinome atlas, elucidates potential targets for developing fat-depot-specific anti-obesity therapies, and offers novel insights into the functional heterogeneity of adipose tissues.