Contribution of the co-chaperone FKBP51 in the ventromedial hypothalamus to 
metabolic homeostasis in male and female mice

Brix, Lea; Toksöz, Irmak; Aman, London; Kovarova, Veronika; Springer, Margherita; Bordes, Joeri; van Doeselaar, Lotte; Engelhardt, Clara; Haeusl, Alexander S; Narayan, Sowmya; Sterlemann, Vera; Yang, Huanqing; Deussing, Jan M.; Schmidt, Mathias V.

doi:10.1016/j.molmet.2022.101579

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Contribution of the co-chaperone FKBP51 in the ventromedial hypothalamus to metabolic homeostasis in male and female mice

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/persons/resource/persons261977

Brix, Lea
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons276145

Toksöz, Irmak
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons287955

Aman, London
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons287957

Kovarova, Veronika
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons262511

Springer, Margherita
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons261974

Bordes, Joeri
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons261970

van Doeselaar, Lotte
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons207257

Engelhardt, Clara
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons135680

Haeusl, Alexander S
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons262411

Narayan, Sowmya
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons276150

Sterlemann, Vera
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons261972

Yang, Huanqing
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80301

Deussing, Jan M.
RG Molecular Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80514

Schmidt, Mathias V.
RG Stress Resilience, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Brix, L., Toksöz, I., Aman, L., Kovarova, V., Springer, M., Bordes, J., et al. (2022). Contribution of the co-chaperone FKBP51 in the ventromedial hypothalamus to metabolic homeostasis in male and female mice. MOLECULAR METABOLISM, 65: 101579. doi:10.1016/j.molmet.2022.101579.

Cite as: https://hdl.handle.net/21.11116/0000-000C-CF3E-7

Abstract

Objective: Steroidogenic factor 1 (SF1) expressing neurons in the ventromedial hypothalamus (VMH) have been directly implicated in whole-body metabolism and in the onset of obesity. The co-chaperone FKBP51 is abundantly expressed in the VMH and was recently linked to type 2 diabetes, insulin resistance, adipogenesis, browning of white adipose tissue (WAT) and bodyweight regulation.
Methods: We investigated the role of FKBP51 in the VMH by conditional deletion and virus-mediated overexpression of FKBP51 in SF1-positive neurons. Baseline and high fat diet (HFD)-induced metabolic- and stress-related phenotypes in male and female mice were obtained.
Results: In contrast to previously reported robust phenotypes of FKBP51 manipulation in the entire mediobasal hypothalamus (MBH), selective deletion or overexpression of FKBP51 in the VMH resulted in only a moderate alteration of HFD-induced bodyweight gain and body composition, independent of sex.
Conclusions: Overall, this study shows that animals lacking and overexpressing Fkbp5 in Sf1-expressing cells within the VMH display only a mild metabolic phenotype compared to an MBH-wide manipulation of this gene, suggesting that FKBP51 in SF1 neurons within this hypothalamic nucleus plays a subsidiary role in controlling whole-body metabolism. (c) 2022 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).