FKBP51 and the molecular chaperoning of metabolism

The molecular chaperone FK506-binding protein 51 (FKBP51) is gaining attention as a meaningful biomarker of metabolic dysfunction. This review examines the emerging contributions of FKBP51 in adipogenesis and lipid metabolism, myogenesis and protein catabolism, and glucocorticoid-induced skin hypoplasia and dermal adipocytes. The FKBP51 signaling mechanisms that may explain these metabolic consequences are discussed. These mechanisms are diverse, with FKBP51 independently and directly regulating phosphorylation cascades and nuclear receptors. We provide a discussion of the newly developed compounds that antagonize FKBP51, which may offer therapeutic advantages for adiposity. These observations suggest we are only beginning to uncover the complex nature of FKBP51 and its molecular chaperoning of metabolism. FK506-binding protein 51 (FKBP51) expression is highest in adipose tissue, increases with adipogenesis, and is associated with obesity in rodents and humans.FKBP51 is a multifunctional protein that regulates several metabolic processes that control adiposity.FKBP51 directly interacts with the insulin receptor signaling cascade to induce insulin resistance.The antagonism of FKBP51 is a promising target in the prevention or treatment of obesity and diabetes.