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

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

doi:10.1016/j.molmet.2022.101579

Molecular Metabolism

2022

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

Lea M. Brix¹,

Irmak Toksöz²,

London Aman³

et al.

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Cited by 4 publications

(1 citation statement)

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“…Moreover, pharmacological modulation of FKBP51 or genetic manipulation of Fkbp5 in rodents has already demonstrated its implications in stress resilience mechanisms ( 19 , 20 , 24 – 27 ). However, the contribution of FKBP51 to stress resilience processes may vary largely between different brain regions, or even so, between specific cell types, which has already been highlighted by previous work from our group and others ( 25 – 31 ).…”

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confidence: 55%

Sex-specific and opposed effects of FKBP51 in glutamatergic and GABAergic neurons: Implications for stress susceptibility and resilience

van Doeselaar,

Stark,

Mitra

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Mental health disorders often arise as a combination of environmental and genetic factors. The FKBP5 gene, encoding the GR co-chaperone FKBP51, has been uncovered as a key genetic risk factor for stress-related illness. However, the exact cell type and region-specific mechanisms by which FKBP51 contributes to stress resilience or susceptibility processes remain to be unravelled. FKBP51 functionality is known to interact with the environmental risk factors age and sex, but so far data on behavioral, structural, and molecular consequences of these interactions are still largely unknown. Here we report the cell type- and sex-specific contribution of FKBP51 to stress susceptibility and resilience mechanisms under the high-risk environmental conditions of an older age, by using two conditional knockout models within glutamatergic ( Fkbp5 Nex ) and GABAergic ( Fkbp5 Dlx ) neurons of the forebrain. Specific manipulation of Fkbp51 in these two cell types led to opposing effects on behavior, brain structure and gene expression profiles in a highly sex-dependent fashion. The results emphasize the role of FKBP51 as a key player in stress-related illness and the need for more targeted and sex-specific treatment strategies.

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mentioning

confidence: 55%

Sex-specific and opposed effects of FKBP51 in glutamatergic and GABAergic neurons: Implications for stress susceptibility and resilience

van Doeselaar,

Stark,

Mitra

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Genetically engineered mouse models of FK506‐binding protein 5

Gebru

Hill

Blair

2023

J of Cellular Biochemistry

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FK506 binding protein 51 (FKBP51) is a molecular chaperone that influences stress response. In addition to having an integral role in the regulation of steroid hormone receptors, including glucocorticoid receptor, FKBP51 has been linked with several biological processes including metabolism and neuronal health. Genetic and epigenetic alterations in the gene that encodes FKBP51, FKBP5, are associated with increased susceptibility to multiple neuropsychiatric disorders, which has fueled much of the research on this protein. Because of the complexity of these processes, animal models have been important in understanding the role of FKBP51. This review examines each of the current mouse models of FKBP5, which include whole animal knockout, conditional knockout, overexpression, and humanized mouse models. The generation of each model and observational details are discussed, including behavioral phenotypes, molecular changes, and electrophysiological alterations basally and following various challenges. While much has been learned through these models, there are still many aspects of FKBP51 biology that remain opaque and future studies are needed to help illuminate these current gaps in knowledge. Overall, FKBP5 continues to be an exciting potential target for stress‐related disorders.

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FKBP51 Overexpression in the Corticolimbic System Stabilizes Circadian Rhythms

Gebru,

Beaulieu-Abdelahad,

Gulick

et al. 2024

Cell Stress and Chaperones

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

Cited by 4 publications

References 51 publications

Sex-specific and opposed effects of FKBP51 in glutamatergic and GABAergic neurons: Implications for stress susceptibility and resilience

Sex-specific and opposed effects of FKBP51 in glutamatergic and GABAergic neurons: Implications for stress susceptibility and resilience

Genetically engineered mouse models of FK506‐binding protein 5

FKBP51 Overexpression in the Corticolimbic System Stabilizes Circadian Rhythms

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