Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease-Reference-Cited by-同舟云学术

Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease

Published:2022-03 Issue:10 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Jouffe Céline¹²³^ORCID,Weger Benjamin D.¹⁴^ORCID,Martin Eva¹,Atger Florian¹²^ORCID,Weger Meltem⁴^ORCID,Gobet Cédric¹⁵^ORCID,Ramnath Divya⁴^ORCID,Charpagne Aline¹,Morin-Rivron Delphine¹^ORCID,Powell Elizabeth E.⁶⁷,Sweet Matthew J.⁴^ORCID,Masoodi Mojgan¹⁸^ORCID,Uhlenhaut N. Henriette³⁹^ORCID,Gachon Frédéric¹⁴⁵^ORCID

Affiliation:

1. Nestlé Research, Société des Produits Nestlé, CH-1015 Lausanne, Switzerland

2. Department of Pharmacology and Toxicology, University of Lausanne, CH-1011 Lausanne, Switzerland

3. Helmholtz Diabetes Center, Helmholtz Zentrum München, DE-85764 Neuherberg, Germany

4. Institute for Molecular Bioscience, The University of Queensland, St. Lucia QLD 4072, Australia

5. School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

6. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane QLD 4102, Australia

7. Faculty of Medicine, Center for Liver Disease Research, Translational Research Institute, The University of Queensland, Brisbane QLD 4102, Australia

8. Institute of Clinical Chemistry, Bern University Hospital, Bern 3010, Switzerland

9. Metabolic Programming, Technical University of Munich School of Life Sciences, DE-85354 Freising, Germany

Abstract

Significance While increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases.

Funder

EC | FP7 | FP7 Ideas: European Research Council

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Deutsche Forschungsgemeinschaft

Department of Health | National Health and Medical Research Council

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2200083119

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