Cold-induced serum amyloid A3 amplifies cAMP–PKA signaling to drive adaptive thermogenesis in brown adipocytes

The global rise in obesity and its associated comorbidities, including type 2 diabetes and cardiovascular disease, presents a major public health challenge. Adipose tissue plays a central role in maintaining energy homeostasis and is a key contributor to the development of obesity and related metabolic disorders [ 1 ]. Among these, brown adipose tissue (BAT) has garnered considerable attention due to its capacity to dissipate energy by promoting triglyceride clearance, glucose uptake, and heat generation through thermogenesis [ 2 , 3 ]. The thermogenic function of BAT is primarily driven by mitochondrial uncoupling protein 1 (UCP1), which uncouples oxidative phosphorylation to produce heat instead of ATP. UCP1-mediated adaptive thermogenesis not only contributes to body temperature regulation but also enhances overall energy expenditure [ 3 , 4 , 5 ]. The discovery of active BAT in adult humans has sparked intense interest in its potential as a therapeutic target for obesity and metabolic disease by promoting energy dissipation and limiting weight gain.