The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus

Häusl, Alexander S.; Hartmann, Jakob; Pöhlmann, Max L.; Brix, Lea M.; Lopez, Juan-Pablo; Brivio, Elena; Engelhardt, Clara; Roeh, Simone; Rudolph, Lisa; Stoffel, Rainer; Hafner, Kathrin; Goss, Hannah M.; Reul, Johannes M. H. M.; Deussing, Jan M.; Ressler, Kerry J.; Gassen, Nils C.; Chen, Alon; Schmidt, Mathias

doi:10.1101/824664

Cited by 2 publications

(2 citation statements)

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“…All animals were fed with a standard research chow diet (Altromin 1318, Altromin GmbH, Germany) or a high fat diet (HFD, 58% kcal from fat, D12331, Research Diets, New Brunswick, NJ, USA). For all experiments, male C57Bl/6n or male Fkbp5 lox/lox mice (described in Ref 67 ) aged between 2-5 months were used.…”

Section: Discussionmentioning

confidence: 99%

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism

Bajaj

et al. 2021

Preprint

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The mediobasal hypothalamus (MBH) is the central region in the physiological response to metabolic stress. The FK506-binding protein 51 (FKBP51) is a major modulator of the stress response and has recently emerged as a scaffolder regulating metabolic and autophagy pathways. However, the detailed protein-protein interactions linking FKBP51 to autophagy upon metabolic challenges remain elusive. We performed mass spectrometry-based metabolomics of FKBP51 knockout (KO) cells revealing an increased amino acid and polyamine metabolism. We identified FKBP51 as a central nexus for the recruitment of the LKB1/AMPK complex to WIPI4 and TSC2 to WIPI3, thereby regulating the balance between autophagy and mTOR signaling in response to metabolic challenges. Furthermore, we demonstrated that MBH FKBP51 deletion strongly induces obesity, while its overexpression protects against high-fat diet (HFD) induced obesity. Our study provides an important novel regulatory function of MBH FKBP51 within the stress-adapted autophagy response to metabolic challenges.

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Section: Discussionmentioning

confidence: 99%

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism

Bajaj

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…All animals were fed with a standard research chow diet (Altromin 1318, Altromin GmbH, Germany) or an HFD (58% kcal from fat; D12331, Research Diets, New Brunswick, NJ, USA). For all experiments, male C57BL/6N or male Fkbp5 lox/lox mice [described in ( 65 )] aged between 2 and 5 months were used.…”

Section: Methodsmentioning

confidence: 99%

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism

et al. 2022

Self Cite

View full text Add to dashboard Cite

The mediobasal hypothalamus (MBH) is the central region in the physiological response to metabolic stress. The FK506-binding protein 51 (FKBP51) is a major modulator of the stress response and has recently emerged as a scaffolder regulating metabolic and autophagy pathways. However, the detailed protein-protein interactions linking FKBP51 to autophagy upon metabolic challenges remain elusive. We performed mass spectrometry–based metabolomics of FKBP51 knockout (KO) cells revealing an increased amino acid and polyamine metabolism. We identified FKBP51 as a central nexus for the recruitment of the LKB1/AMPK complex to WIPI4 and TSC2 to WIPI3, thereby regulating the balance between autophagy and mTOR signaling in response to metabolic challenges. Furthermore, we demonstrated that MBH FKBP51 deletion strongly induces obesity, while its overexpression protects against high-fat diet (HFD)–induced obesity. Our study provides an important novel regulatory function of MBH FKBP51 within the stress-adapted autophagy response to metabolic challenges.

show abstract

The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus

Cited by 2 publications

References 44 publications

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism

Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism

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