Rev1 deficiency induces replication stress to cause metabolic dysfunction differently in males and females

American Journal of Physiology-Endocrinology and Metabolism, vol. 322, pp. E319–E329

Abstract

An increasing number of DNA lesions interferes with cellular replication leading to metabolic inflexibility. We utilized Rev1 knockout mice as a model for replication stress, and show a sex-dependent metabolic phenotype, with a pronounced reduction of lean mass and glucose tolerance. These data indicate that in obesity, we may end up in an infinite loop where metabolic disturbance promotes the formation of DNA lesions, which in turn interferes with cellular replication causing further metabolic disturbances.

Authors 12

1. Wietse In het Panhuis corresponding Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

2. Anastasia Tsaalbi‐Shtylik Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

3. Milena Schönke Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

4. Vanessa van Harmelen Aachen Department of Human Genetics Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

5. Amanda C. M. Pronk Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

6. Trea C.M. Streefland Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

7. Hetty C. M. Sips Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

8. Salwa Afkir Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

9. Ko Willems van Dijk Aachen Department of Human Genetics Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

10. Patrick C.N. Rensen Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

    Leiden University Medical Center

    Affiliation as printed

    Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

11. Niels de Wind Aachen Department of Human Genetics

    Leiden University Medical Center

    Affiliation as printed

    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

12. Sander Kooijman Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

    Leiden University Medical Center

    Affiliation as printed

    Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands