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

Ye R, Holland WL, Gordillo R, Wang M, Wang QA, Shao M, Morley TS, Gupta RK, Stahl A, Scherer PE - Elife (2014)

Bottom Line: As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects.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.

View Article: PubMed Central - PubMed

Affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 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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Hepatic secretion rates of triglycerides.Slopes of plasma triglyceride over time after tyloxapol injection. n = 7–9 mice per condition. Data are presented as the mean ± SEM. Related to Figure 2F.DOI:http://dx.doi.org/10.7554/eLife.03851.012
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fig2s4: Hepatic secretion rates of triglycerides.Slopes of plasma triglyceride over time after tyloxapol injection. n = 7–9 mice per condition. Data are presented as the mean ± SEM. Related to Figure 2F.DOI:http://dx.doi.org/10.7554/eLife.03851.012

Mentions: We wanted to determine what the underlying mechanisms are for the exacerbated lipid metabolism in STZ-treated adiponectin knockout mice. We addressed whether changes in hepatic lipid secretion may be the underlying reason. We treated the mice with the lipoprotein lipase inhibitor tyloxapol (WR-1339) and monitored serum lipid accumulation, a classical test to assess VLDL secretion. Compared to WT control mice, adiponectin mice demonstrated only a minor trend towards an increase in serum triglyceride content (Figure 2F) and rate of accumulation (Figure 2—figure supplement 4). We also examined a panel of metabolic gene expression in the livers of STZ-treated Adn+/+ and Adn−/− mice and observed no significant changes (Figure 2—figure supplement 5).


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

Ye R, Holland WL, Gordillo R, Wang M, Wang QA, Shao M, Morley TS, Gupta RK, Stahl A, Scherer PE - Elife (2014)

Hepatic secretion rates of triglycerides.Slopes of plasma triglyceride over time after tyloxapol injection. n = 7–9 mice per condition. Data are presented as the mean ± SEM. Related to Figure 2F.DOI:http://dx.doi.org/10.7554/eLife.03851.012
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4228265&req=5

fig2s4: Hepatic secretion rates of triglycerides.Slopes of plasma triglyceride over time after tyloxapol injection. n = 7–9 mice per condition. Data are presented as the mean ± SEM. Related to Figure 2F.DOI:http://dx.doi.org/10.7554/eLife.03851.012
Mentions: We wanted to determine what the underlying mechanisms are for the exacerbated lipid metabolism in STZ-treated adiponectin knockout mice. We addressed whether changes in hepatic lipid secretion may be the underlying reason. We treated the mice with the lipoprotein lipase inhibitor tyloxapol (WR-1339) and monitored serum lipid accumulation, a classical test to assess VLDL secretion. Compared to WT control mice, adiponectin mice demonstrated only a minor trend towards an increase in serum triglyceride content (Figure 2F) and rate of accumulation (Figure 2—figure supplement 4). We also examined a panel of metabolic gene expression in the livers of STZ-treated Adn+/+ and Adn−/− mice and observed no significant changes (Figure 2—figure supplement 5).

Bottom Line: As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects.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.

View Article: PubMed Central - PubMed

Affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 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.

Show MeSH
Related in: MedlinePlus