Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration
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...
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2014-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/03851 |
| _version_ | 1811180484146757632 |
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| author | Risheng Ye William L Holland Ruth Gordillo Miao Wang Qiong A Wang Mengle Shao Thomas S Morley Rana K Gupta Andreas Stahl Philipp E Scherer |
| author_facet | Risheng Ye William L Holland Ruth Gordillo Miao Wang Qiong A Wang Mengle Shao Thomas S Morley Rana K Gupta Andreas Stahl Philipp E Scherer |
| author_sort | Risheng Ye |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:03:53Z |
| format | Article |
| id | doaj.art-83bf4796034b481d9eb90f452d20685e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:03:53Z |
| publishDate | 2014-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-83bf4796034b481d9eb90f452d20685e2022-12-22T04:32:42ZengeLife Sciences Publications LtdeLife2050-084X2014-10-01310.7554/eLife.03851Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regenerationRisheng Ye0William L Holland1Ruth Gordillo2Miao Wang3Qiong A Wang4Mengle Shao5Thomas S Morley6Rana K Gupta7Andreas Stahl8Philipp E Scherer9Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, United StatesTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, United States; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United StatesAs 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.https://elifesciences.org/articles/03851adiponectininsulin deficiencylipid metabolismislet lipotoxicityβ-cell regeneration |
| spellingShingle | Risheng Ye William L Holland Ruth Gordillo Miao Wang Qiong A Wang Mengle Shao Thomas S Morley Rana K Gupta Andreas Stahl Philipp E Scherer Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration eLife adiponectin insulin deficiency lipid metabolism islet lipotoxicity β-cell regeneration |
| title | Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration |
| title_full | Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration |
| title_fullStr | Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration |
| title_full_unstemmed | Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration |
| title_short | Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration |
| title_sort | adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β cell regeneration |
| topic | adiponectin insulin deficiency lipid metabolism islet lipotoxicity β-cell regeneration |
| url | https://elifesciences.org/articles/03851 |
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