Research Paper Advance Articles pp 24156—24167

Gut microbiota transplantation from db/db mice induces diabetes-like phenotypes and alterations in Hippo signaling in pseudo germ-free mice

Fan Yu1, *, , Riyue Jiang2, *, , Wei Han3, , Gaofeng Zhan4, , Xiaolin Xu4, , Xiaohong Jiang1, , Long Wang1, , Shoukui Xiang1, , Qin Zhou2, , Cunming Liu5, , Bin Zhu6, , Fei Hua1, , Chun Yang5, ,

  • 1 Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
  • 2 Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • 3 Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
  • 4 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 5 Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • 6 Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
* Equal contribution

Received: April 14, 2020       Accepted: September 4, 2020       Published: November 20, 2020      

https://doi.org/10.18632/aging.104101
How to Cite

Copyright: © 2020 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Type 2 diabetes mellitus (T2DM) is an age-related metabolic disease that is of increasing concern. Gut microbiota might have a critical role in the pathogenesis of T2DM. Additionally, Hippo signaling has been associated strongly with the progression of T2DM and the aging process. We adopted db/db male mice as a T2DM model, and the gut microbiota of db/db and m/m mice were transplanted successfully into pseudo germ-free mice. Furthermore, Hippo signaling, including mammalian sterile 20-like protein kinases 1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP), and phosphorylation of YAP (p-YAP) in peripheral tissues were significantly altered and highly correlated with blood glucose in db/db mice. Interestingly, the host after gut microbiota transplantation from db/db mice showed decreased MST1 and LATS1 levels, and p-YAP/YAP ratio in the heart, liver, and kidney compared to those from m/m mice. Negative correlations between fasting blood glucose and Hippo signaling levels in selected peripheral tissues also were identified. These findings suggest that alterations in Hippo signaling in selected peripheral tissues may contribute to the development of T2DM, and that therapeutic interventions improving Hippo signaling by gut microbiota transplantation might be beneficial for the treatment of T2DM and other age-related metabolic diseases.

Abbreviations

AD: Alzheimer’s disease; LATS1: large tumor suppressors 1; MST1: mammalian sterile 20-like protein kinases 1; p-YAP: phosphorylation of Yes-associated protein; T2DM: type 2 diabetes mellitus; YAP: Yes-associated protein.