Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration
- University of Texas Southwestern Medical Center, United States
- 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.
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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).
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© 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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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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