Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration

  1. Risheng Ye
  2. William L Holland
  3. Ruth Gordillo
  4. Miao Wang
  5. Qiong A Wang
  6. Mengle Shao
  7. Thomas S Morley
  8. Rana K Gupta
  9. Andreas Stahl
  10. Philipp E Scherer  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. University of California Berkeley, United States

Abstract

As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects. While many important functions have been attributed to adiponectin under high-fat diet conditions, little is known about its essential role under regular chow. Employing a mouse model with inducible, acute β-cell ablation, we uncovered an essential role of adiponectin under insulinopenic conditions to maintain minimal lipid homeostasis. When insulin levels are marginal, adiponectin is critical for insulin signaling, endocytosis and lipid uptake in subcutaneous white adipose tissue. In the absence of both insulin and adiponectin, severe lipoatrophy and hyperlipidemia lead to lethality. In contrast, elevated adiponectin levels improve systemic lipid metabolism in the near absence of insulin. Moreover, adiponectin is sufficient to mitigate local lipotoxicity in pancreatic islets, and it promotes reconstitution of β-cell mass, eventually reinstating glycemic control. We uncovered an essential new role for adiponectin, with major implications for type 1 diabetes.

Article and author information

Author details

  1. Risheng Ye

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. William L Holland

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

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Miao Wang

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Qiong A Wang

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Mengle Shao

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Thomas S Morley

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Rana K Gupta

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Andreas Stahl

    University of California Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Philipp E Scherer

    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.

Ethics

Animal experimentation: All protocols for mouse use and euthanasia were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Texas Southwestern Medical Center (#2010-0006).

Reviewing Editor

  1. Peter Tontonoz, University of California, Los Angeles, United States

Version history

  1. Received: July 3, 2014
  2. Accepted: October 15, 2014
  3. Accepted Manuscript published: October 23, 2014 (version 1)
  4. Version of Record published: November 12, 2014 (version 2)

Copyright

© 2014, Ye 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.

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  1. Risheng Ye
  2. William L Holland
  3. Ruth Gordillo
  4. Miao Wang
  5. Qiong A Wang
  6. Mengle Shao
  7. Thomas S Morley
  8. Rana K Gupta
  9. Andreas Stahl
  10. Philipp E Scherer
(2014)
Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration
eLife 3:e03851.
https://doi.org/10.7554/eLife.03851

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