Loss of FKBP5 impedes adipocyte differentiation under both normoxia and hypoxic stress.

Abstract

FK506-binding protein 51 (FKBP51) is one of the most important regulators in the GR-mediated stress response, and we previously demonstrated that loss of FKBP5 arrests adipogenesis and renders mice resistant to diet-induced obesity (DIO). However, the exact role of FKBP5 in the process of adipocyte differentiation under hypoxic conditions (the common microenvironment where adipocytes reside in obese individuals) is still unclear. Here, by isolating and culturing WT- and Fkbp5-knockout mouse embryonic fibroblasts (MEFs), and treat them at normal oxygen environment (21% O2, nomorxia) or low oxygen environment (5% O2, hypoxia). Enhanced adipogenesis were observed at hypoxia when compared to normal oxygen environment. The loss of FKBP5 significantly prevents the adipogenesis from KO MEFs under nomorxia condition, with subtle enhancement of adipogenesis at hypoxia condition, which is similar as observed in WT-MEFs at hypoxia condition but with obvious enhancement of adipogenesis. Importantly, the protein level of FKBP5 reduced in undifferentiated MEFs under acute hypoxic stress (24 h), but drastically increased during the mid-late stage of adipocyte (Day 6) differentiation from WT-MEFs under chronic hypoxia. Furthermore, we find under normal and hypoxic conditions that FKBP5 deletion alters the expression profile of adipogenesis-related genes, including those involved in lipogenesis, lipolysis, and energy metabolism, which partially explains the compromised adipocyte differentiation in FKBP51-KO MEFs. Taken together, our findings identify a novel role of FKBP5 in hypoxia-regulated adipogenesis, and provide a candidate for anti-obesity strategies targeting FKBP51.

• Authors: Lingling Zhang, Bin Qiu, Tingting Wang, Jun Wang, Ming Liu, Yuxue Xu, Chao Wang, Ran Deng, Kent Williams, Zhiwei Yang, Tiebing Liang, Weidong Yong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 485 Issue 4 Pg. 761-767 (04 15 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 28254433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Adiponectin
• CD36 Antigens
• Ucp1 protein, mouse
• Uncoupling Protein 1
• Tacrolimus Binding Proteins
• tacrolimus binding protein 5

Topics

• Adipocytes (metabolism)
• Adipogenesis (genetics)
• Adiponectin (genetics)
• Animals
• Blotting, Western
• CD36 Antigens (genetics)
• Cell Differentiation (genetics)
• Cell Hypoxia
• Cells, Cultured
• Embryo, Mammalian (cytology)
• Fibroblasts (metabolism)
• Gene Expression Profiling (methods)
• Mice, Knockout
• Reverse Transcriptase Polymerase Chain Reaction
• Tacrolimus Binding Proteins (genetics, metabolism)
• Time Factors
• Uncoupling Protein 1 (genetics)