FKBP51 and the molecular chaperoning of metabolism.

Kathryn B Smedlund, Edwin R Sanchez, Terry D Hinds

Journal: Trends in endocrinology and metabolism: TEM 2022;32(11):862-874

PMID: 34481731

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Abstract

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.

Address: Center for Diabetes and Endocrine Research, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.; Barnstable Brown Diabetes Center, Markey Cancer Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40508, USA. Electronic address: [email protected].

DOI: 10.1016/j.tem.2021.08.003

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MeSH Terms: Glucocorticoids, Humans, Molecular Chaperones, Phosphorylation, Receptors, Glucocorticoid, Tacrolimus Binding Proteins