Focus on FKBP51: A molecular link between stress and metabolic disorders

Alexander S. Häusl, Georgia Balsevich, Nils C. Gassen, Mathias V. Schmidt

Background: Obesity, Type 2 diabetes (T2D) as well as stress-related disorders are rising public health threats and major burdens for modern society. Chronic stress and depression are highly associated with symptoms of the metabolic syndrome, but the molecular link is still not fully understood. Furthermore, therapies tackling these biological disorders are still lacking. The identification of shared molecular targets underlying both pathophysiologies may lead to the development of new treatments. The FK506 binding protein 51 (FKBP51) has recently been identified as a promising therapeutic target for stress-related psychiatric disorders and obesity-related metabolic outcomes.

Scope of review: The aim of this review is to summarize current evidence of in vitro, preclinical, and human studies on the stress responsive protein FKBP51, focusing on its newly discovered role in metabolism. Also, we highlight the therapeutic potential of FKBP51 as a new treatment target for symptoms of the metabolic syndrome.

Major conclusions: We conclude the review by emphasizing missing knowledge gaps that remain and future research opportunities needed to implement FKBP51 as a drug target for stress-related obesity or T2D.