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Relation of adipose tissue and skeletal muscle FKBP5 expression with insulin sensitivity and the regulation of FKBP5 by insulin and free fatty acids

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Abstract

Purpose

Recent studies suggest that FK506 binding protein 51 (FKBP51), a negative regulator of glucocorticoid response, encoded by FKBP5, may influence insulin action. The aim of the present study was to assess the relationship between subcutaneous adipose tissue (AT) and skeletal muscle FKBP5 expression in relation to insulin sensitivity in healthy individuals and to study its regulation by insulin and circulating free fatty acid (FFA) elevation.

Methods

The study group comprised 96 male subjects, 49 normal-weight and 47 overweight/obese. Hyperinsulinemic clamp, subcutaneous AT and skeletal muscle biopsies were performed. In a subgroup of 20 subjects, two 6 h clamps were performed, with and without Intralipid/heparin infusion, and tissue biopsies were obtained before and after each clamp.

Results

AT FKBP5 expression was lower in overweight/obese individuals in comparison with normal-weight individuals (p = 0.004). Muscle FKBP5 expression did not differ between the groups, however, it was inversely related to insulin sensitivity (r = −0.32, p = 0.002). FKBP5 expression decreased in AT (p = 0.003) and increased in muscle (p < 0.0001) after insulin infusion. Intralipid/heparin diminished insulin-induced increase in muscle FKBP5.

Conclusion

Our data show that lower AT FKBP5 expression is related to obesity, whereas muscle FKBP5 expression is associated with insulin resistance. AT and muscle FKBP5 expression is differentially regulated by insulin.

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Data availability

Data from the present study are available from the corresponding author upon reasonable request.

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Acknowledgements

Supported by The Grant UDA-POIG.01.03.01-00-128/08; from the Program Innovative Economy 2007-2013; part-financed by the European Union within the European Regional Development Fund.

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Authors and Affiliations

  1. Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland

    Marek Strączkowski & Agnieszka Nikołajuk

  2. Department of Metabolic Diseases, Medical University of Białystok, Białystok, Poland

    Magdalena Stefanowicz & Natalia Matulewicz

  3. Department of Internal Medicine and Metabolic Diseases, Medical University of Białystok, Białystok, Poland

    Monika Karczewska-Kupczewska

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  1. Marek Strączkowski
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Correspondence to Marek Strączkowski.

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A written informed consent was obtained from all individual participants included in the study.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the local ethics committee of the Medical University of Białystok.

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Strączkowski, M., Stefanowicz, M., Matulewicz, N. et al. Relation of adipose tissue and skeletal muscle FKBP5 expression with insulin sensitivity and the regulation of FKBP5 by insulin and free fatty acids. Endocrine 76, 536–542 (2022). https://doi.org/10.1007/s12020-022-03018-7

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