Adiponectin preserves metabolic fitness during aging

  1. Na Li
  2. Shangang Zhao
  3. Zhuzhen Zhang
  4. Yi Zhu
  5. Christy M Gliniak
  6. Lavanya Vishvanath
  7. Yu A An
  8. May-yun Wang
  9. Yingfeng Deng
  10. Qingzhang Zhu
  11. Bo Shan
  12. Amber Sherwood
  13. Toshiharu Onodera
  14. Orhan K Oz
  15. Ruth Gordillo
  16. Rana K Gupta
  17. Ming Liu
  18. Tamas L Horvath
  19. Vishwa Deep Dixit
  20. Philipp E Scherer  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. Baylor College of Medicine, United States
  3. Tianjin Medical University General Hospital, China
  4. Yale University School of Medicine, United States

Abstract

Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet (HFD). In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Na Li

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Shangang Zhao

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9209-8206
  3. Zhuzhen Zhang

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yi Zhu

    Department of Pediatric, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Christy M Gliniak

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lavanya Vishvanath

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yu A An

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. May-yun Wang

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Yingfeng Deng

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1314-5105
  10. Qingzhang Zhu

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Bo Shan

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Amber Sherwood

    Radiology - RA-Lab Nuclear Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Toshiharu Onodera

    Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Orhan K Oz

    Department of Radiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Ruth Gordillo

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Rana K Gupta

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9001-4531
  17. Ming Liu

    Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
    Competing interests
    The authors declare that no competing interests exist.
  18. Tamas L Horvath

    Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7522-4602
  19. Vishwa Deep Dixit

    Comparative Medicine and Immunobiology, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5341-6494
  20. Philipp E Scherer

    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    philipp.scherer@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0680-3392

Funding

National Institutes of Health (P01-AG051459)

  • Philipp E Scherer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Li et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Na Li
  2. Shangang Zhao
  3. Zhuzhen Zhang
  4. Yi Zhu
  5. Christy M Gliniak
  6. Lavanya Vishvanath
  7. Yu A An
  8. May-yun Wang
  9. Yingfeng Deng
  10. Qingzhang Zhu
  11. Bo Shan
  12. Amber Sherwood
  13. Toshiharu Onodera
  14. Orhan K Oz
  15. Ruth Gordillo
  16. Rana K Gupta
  17. Ming Liu
  18. Tamas L Horvath
  19. Vishwa Deep Dixit
  20. Philipp E Scherer
(2021)
Adiponectin preserves metabolic fitness during aging
eLife 10:e65108.
https://doi.org/10.7554/eLife.65108

Share this article

https://doi.org/10.7554/eLife.65108

Further reading

    1. Cell Biology
    Yan Song, Linda J Fothergill ... Gene W Yeo
    Research Article

    Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.