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Focus on FKBP51: A molecular link between stress and metabolic disorders.

ABSTRACT: BACKGROUND:Obesity, Type 2 diabetes (T2D) as well as stress-related disorders are rising public health threats and major burdens for modern society. Chronic stress and depression are highly associated with symptoms of the metabolic syndrome, but the molecular link is still not fully understood. Furthermore, therapies tackling these biological disorders are still lacking. The identification of shared molecular targets underlying both pathophysiologies may lead to the development of new treatments. The FK506 binding protein 51 (FKBP51) has recently been identified as a promising therapeutic target for stress-related psychiatric disorders and obesity-related metabolic outcomes. SCOPE OF THE REVIEW:The aim of this review is to summarize current evidence of in vitro, preclinical, and human studies on the stress responsive protein FKBP51, focusing on its newly discovered role in metabolism. Also, we highlight the therapeutic potential of FKBP51 as a new treatment target for symptoms of the metabolic syndrome. MAJOR CONCLUSIONS:We conclude the review by emphasizing missing knowledge gaps that remain and future research opportunities needed to implement FKBP51 as a drug target for stress-related obesity or T2D.

SUBMITTER: Hausl AS

PROVIDER: S-EPMC6812026 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Focus on FKBP51: A molecular link between stress and metabolic disorders.

Häusl Alexander S AS Balsevich Georgia G Gassen Nils C NC Schmidt Mathias V MV

Molecular metabolism 20190911

<h4>Background</h4>Obesity, Type 2 diabetes (T2D) as well as stress-related disorders are rising public health threats and major burdens for modern society. Chronic stress and depression are highly associated with symptoms of the metabolic syndrome, but the molecular link is still not fully understood. Furthermore, therapies tackling these biological disorders are still lacking. The identification of shared molecular targets underlying both pathophysiologies may lead to the development of new tr ...[more]

PMID: 31668388

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Project description:The risk of metabolic diseases is greatly increased by both chronic and acute stress. Irrespective of the cause, chronic or acute stress has the capacity to alter an individual's cytokine profile. For instance, it has been observed that stress significantly increased concentrations of IL 1 beta, IL 6 and TNF alpha. Alteration in cytokine profiles increase the likelihood of dysregulated metabolism, which subsequently acts as a driving force in the development of disorders, such as cardiovascular disease (CVD), hypertension, diabetes and obesity. Considering the dynamic and versatile role of cytokines in health and disease, an in-depth computational analysis (qualitative and quantitative) was performed to study the role of cytokines as an immuno-molecular link between rising stress levels and an increase in CVD, hypertension, diabetes and obesity. Upon a qualitative comparative analysis of cytokine profiles, a total of 14 cytokines (IL-6, TNF-alpha, IFN-gamma, IL-10, etc.) were observed to be commonly involved in stress and aforementioned four metabolic disorders. Further analysis of quantitative studies has revealed that the cytokine profile for coronary artery disease (CAD) showed remarkable increase in a couple of cytokines. IL 9 registered an increase of 67 percent to reach a concentration of 75 pg/mL. IL 3, on the other hand, was absent in control candidates but reached 56 ± 14 pg/mL in CAD patients. In case of diabetes, IFN-gamma showed an increase of 290 pg/mL. For obesity it was observed that both MCP-1 and IL-1 beta fell by 12.2 pg/mL to reach 44.4 pg/mL in obese patients. A fall of approximately 50 pg/mL was observed in the concentration of VEGF in obese patients. Similarly, hypertension was marked by reduction in concentration of several cytokines - MCP-1 and VEGF being a couple of them. Apart from performing an analysis of cytokine profiles, an innovative database [Cytokine database of Stress and Metabolic disorders (CdoSM)-https://www.akbi-nsut.co.in/] has also been created comprising cytokines involved in stress and the aforementioned metabolic disorders. Upon accessing the database, a user can find the list cytokines associated with a particular condition along with information on cytokine receptor/s; related research articles; cytokine concentration in control v/s diseased candidates for some specific cytokines and the Uniprot ID for the respective cytokine. Database can be accessed by the link-https://www.akbi-nsut.co.in/.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-022-03375-0.

Dataset Information

Focus on FKBP51: A molecular link between stress and metabolic disorders.

Publications

Focus on FKBP51: A molecular link between stress and metabolic disorders.

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