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FKBP5 expression in human adipose tissue: potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes.
Endocrine. 2018 10; 62(1):116-128.E

Abstract

PURPOSE

Here, we explore the involvement of FKBP51 in glucocorticoid-induced insulin resistance (IR) in human subcutaneous adipose tissue (SAT), including its potential role in type 2 diabetes (T2D). Moreover, we assess the metabolic effects of reducing the activity of FKBP51 using the specific inhibitor SAFit1.

METHODS

Human SAT was obtained by needle biopsies of the lower abdominal region. FKBP5 gene expression was assessed in fresh SAT explants from a cohort of 20 T2D subjects group-wise matched by gender, age and BMI to 20 non-diabetic subjects. In addition, human SAT was obtained from non-diabetic volunteers (20F/9M). SAT was incubated for 24 h with or without the synthetic glucocorticoid dexamethasone and SAFit1. Incubated SAT was used to measure the glucose uptake rate in isolated adipocytes.

RESULTS

FKBP5 gene expression levels in SAT positively correlated with several indices of IR as well as glucose area under the curve during oral glucose tolerance test (r = 0.33, p < 0.05). FKBP5 gene expression levels tended to be higher in T2D subjects compared to non-diabetic subjects (p = 0.088). Moreover, FKBP5 gene expression levels were found to inversely correlate with lipolytic, lipogenic and adipogenic genes. SAFit1 partly prevented the inhibitory effects of dexamethasone on glucose uptake.

CONCLUSIONS

FKBP5 gene expression in human SAT tends to be increased in T2D subjects and is related to elevated glucose levels. Moreover, FKBP5 gene expression is inversely associated with the expression of lipolytic, lipogenic and adipogenic genes. SAFit1 can partly prevent glucose uptake impairment by glucocorticoids, suggesting that FKBP51 might be a key factor in glucocorticoid-induced IR.

Authors+Show Affiliations

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.AstraZeneca R&D, Mölndal, Sweden. Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Institute of Organic Chemistry and Biochemistry, Technical University Darmstadt, Darmstadt, Germany.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden. jan.eriksson@medsci.uu.se.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30032404

Citation

Sidibeh, Cherno O., et al. "FKBP5 Expression in Human Adipose Tissue: Potential Role in Glucose and Lipid Metabolism, Adipogenesis and Type 2 Diabetes." Endocrine, vol. 62, no. 1, 2018, pp. 116-128.
Sidibeh CO, Pereira MJ, Abalo XM, et al. FKBP5 expression in human adipose tissue: potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes. Endocrine. 2018;62(1):116-128.
Sidibeh, C. O., Pereira, M. J., Abalo, X. M., J Boersma, G., Skrtic, S., Lundkvist, P., Katsogiannos, P., Hausch, F., Castillejo-López, C., & Eriksson, J. W. (2018). FKBP5 expression in human adipose tissue: potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes. Endocrine, 62(1), 116-128. https://doi.org/10.1007/s12020-018-1674-5
Sidibeh CO, et al. FKBP5 Expression in Human Adipose Tissue: Potential Role in Glucose and Lipid Metabolism, Adipogenesis and Type 2 Diabetes. Endocrine. 2018;62(1):116-128. PubMed PMID: 30032404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FKBP5 expression in human adipose tissue: potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes. AU - Sidibeh,Cherno O, AU - Pereira,Maria J, AU - Abalo,Xesus M, AU - J Boersma,Gretha, AU - Skrtic,Stanko, AU - Lundkvist,Per, AU - Katsogiannos,Petros, AU - Hausch,Felix, AU - Castillejo-López,Casimiro, AU - Eriksson,Jan W, Y1 - 2018/07/21/ PY - 2018/03/16/received PY - 2018/07/02/accepted PY - 2018/7/23/pubmed PY - 2019/2/20/medline PY - 2018/7/23/entrez KW - Adipose tissue KW - FKBP51 KW - Glucocorticoids KW - Insulin resistance KW - SAFit1 KW - Type 2 diabetes SP - 116 EP - 128 JF - Endocrine JO - Endocrine VL - 62 IS - 1 N2 - PURPOSE: Here, we explore the involvement of FKBP51 in glucocorticoid-induced insulin resistance (IR) in human subcutaneous adipose tissue (SAT), including its potential role in type 2 diabetes (T2D). Moreover, we assess the metabolic effects of reducing the activity of FKBP51 using the specific inhibitor SAFit1. METHODS: Human SAT was obtained by needle biopsies of the lower abdominal region. FKBP5 gene expression was assessed in fresh SAT explants from a cohort of 20 T2D subjects group-wise matched by gender, age and BMI to 20 non-diabetic subjects. In addition, human SAT was obtained from non-diabetic volunteers (20F/9M). SAT was incubated for 24 h with or without the synthetic glucocorticoid dexamethasone and SAFit1. Incubated SAT was used to measure the glucose uptake rate in isolated adipocytes. RESULTS: FKBP5 gene expression levels in SAT positively correlated with several indices of IR as well as glucose area under the curve during oral glucose tolerance test (r = 0.33, p < 0.05). FKBP5 gene expression levels tended to be higher in T2D subjects compared to non-diabetic subjects (p = 0.088). Moreover, FKBP5 gene expression levels were found to inversely correlate with lipolytic, lipogenic and adipogenic genes. SAFit1 partly prevented the inhibitory effects of dexamethasone on glucose uptake. CONCLUSIONS: FKBP5 gene expression in human SAT tends to be increased in T2D subjects and is related to elevated glucose levels. Moreover, FKBP5 gene expression is inversely associated with the expression of lipolytic, lipogenic and adipogenic genes. SAFit1 can partly prevent glucose uptake impairment by glucocorticoids, suggesting that FKBP51 might be a key factor in glucocorticoid-induced IR. SN - 1559-0100 UR - https://www.unboundmedicine.com/medline/citation/30032404/FKBP5_expression_in_human_adipose_tissue:_potential_role_in_glucose_and_lipid_metabolism_adipogenesis_and_type_2_diabetes_ DB - PRIME DP - Unbound Medicine ER -