Increasing energy expenditure is an attractive approach to fighting the worldwide epidemic in obesity and type 2 diabetes. Exercise is an important component of good health and represents the first line of therapy for humans with a variety of metabolic disorders: obesity, diabetes, and nonalcoholic hepatic steatosis. Recent data has shown that exercise, besides using calories to do physical work, also causes an increase in energy expenditure through augmentation in brown fat and the browning of white fat (Fig. 1) (1,2). Indeed, these effects on brown fat could represent part of the longer-lasting benefits of exercise. Figure 1 Recombinant irisin regulates the thermogenic program in fat through ERK and p38 pathways. Recombinant irisin produced in yeast is glycosylated and active. It induces the thermogenic gene program in 3T3-L1 cells and primary subcutaneous adipocytes. In vivo treatments of this recombinant protein in mice show strong anti-obesity effects and improve systematic glucose homeostasis. That brown fat, in all of its dimensions, can improve type 2 diabetes and metabolic health seems to be settled science, at least in experimental animals (3). These cells express UCP1 and have a high mitochondrial content, thereby dissipating chemical energy …