title: Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration.
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.
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Risheng
authors.initials: R
authors.lastname: Ye
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: William L
authors.initials: WL
authors.lastname: Holland
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gordillo
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Qiong A
authors.initials: QA
authors.lastname: Wang
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Mengle
authors.initials: M
authors.lastname: Shao
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Morley
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Rana K
authors.initials: RK
authors.lastname: Gupta
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stahl
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000648:ultrastructure; D052242:Adiponectin / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000172:deficiency* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000633:toxicity; D051379:Mice; D012038:Regeneration / Q000187:drug effects; D013311:Streptozocin; D016019:Survival Analysis
chemical_list: D052242:Adiponectin; D051242:Caveolin 1; D007328:Insulin; D008055:Lipids; D013311:Streptozocin
keywords: adiponectin; cell biology; insulin deficiency; islet lipotoxicity; lipid metabolism; mouse; β-cell regeneration