Globular and Full-Length Adiponectin Induce NO-Dependent Vasodilation in Resistance Arteries of Zucker Lean but Not Zucker Diabetic Fatty Rats

Schmid, Peter; Resch, Markus; Steege, Andreas; Fredersdorf-Hahn, Sabine; Stoelcker, Benjamin; Birner, Christoph; Schach, Christian; Buechler, Christa; Riegger, G. A. J.; Luchner, Andreas; Endemann, Dierk

doi:10.1038/ajh.2010.239

Cited by 44 publications

(45 citation statements)

References 40 publications

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“…Globular adiponectin likewise was shown to increase eNOS activity and additionally stimulate eNOS expression (Hattori et al 2003). Both forms of adiponectin can thus influence vasodilation (Schmid et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Fuerst¹,

Taylor²,

Wright³

et al. 2012

Journal of Endocrinology

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Accelerated atherosclerosis is the primary cardiovascular manifestation of diabetes and correlates inversely with levels of circulating adiponectin, an anti-atherosclerotic adipokine that declines in diabetes. We therefore initiated a study to examine the mechanisms by which adiponectin, a hormone released from adipose tissue, influences the proliferation of vascular smooth muscle cells (SMCs). Addition of adiponectin to quiescent porcine coronary artery SMCs increased both protein and DNA synthesis and concurrently activated ERK1/2 and Akt. By contrast, globular adiponectin, a truncated form of this protein, exhibited anti-mitogenic properties as indicated by the inhibition of protein and DNA synthesis in SMCs stimulated with platelet-derived growth factor (PDGF). Whereas globular adiponectin did not stimulate growth-related signal transduction pathways, it was able to block the PDGF-dependent phosphorylation of eukaryotic elongation factor 2 kinase, a regulator of protein synthesis. Proteolysis of adiponectin with trypsin, which produces globular adiponectin, reversed the growth-stimulating actions of the undigested protein. As the existence of globular adiponectin remains controversial, western blotting was used to establish its presence in rat serum. We found that globular adiponectin was detectable in rat serum, but this result was not obtained with all antibodies. The contrasting properties of adiponectin and its globular form with respect to SMC proliferation suggest that protection against atherosclerosis may therefore be mediated, in part, by the level of globular adiponectin.

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Section: Discussionmentioning

confidence: 99%

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Fuerst¹,

Taylor²,

Wright³

et al. 2012

Journal of Endocrinology

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“…This observation could be expected based on related literature (8,12,36,42) demonstrating insulin sensitizing actions of APPL1 in liver and skeletal muscle. Indeed, APPL1 levels were significantly decreased in endothelium of Zucker diabetic fatty rats (38), and a recent study suggested that chronic exercise in mice increased hepatic APPL1 expression, which, at least in part, accounted for improved insulin sensitivity (28). However, in a human study, there was higher APPL1 expression in type 2 diabetic muscle, and weight loss in these individuals was associated with reduced skeletal muscle APPL1 level (22).…”

Section: E801mentioning

confidence: 89%

APPL1 transgenic mice are protected from high-fat diet-induced cardiac dysfunction

Park

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif 1) has been established as an important mediator of insulin and adiponectin signaling. Here, we investigated the influence of transgenic (Tg) APPL1 overexpression in mice on high-fat diet (HFD)-induced cardiomyopathy in mice. Wild-type (WT) mice fed an HFD for 16 wk showed cardiac dysfunction, determined by echocardiography, with decreased ejection fraction, decreased fractional shortening, and increased end diastolic volume. HFD-fed APPL1 Tg mice were significantly protected from this dysfunction. Speckle tracking echocardiography to accurately assess cardiac tissue deformation strain and wall motion also indicated dysfunction in WT mice and a similar improvement in Tg vs. WT mice on HFD. APPL1 Tg mice had less HFD-induced increase in circulating nonesteridied fatty acid levels and myocardial lipid accumulation. Lipidomic analysis using LC-MS-MS showed HFD significantly increased myocardial contents of distinct ceramide, sphingomyelin, and diacylglycerol (DAG) species, of which increases in C16:0 and C18:0 ceramides plus C16:0 and C18:1 DAGs were attenuated in Tg mice. A glucose tolerance test indicated less peripheral insulin resistance in response to HFD in Tg mice, which was also apparent by measuring cardiac Akt phosphorylation and cardiomyocyte glucose uptake. In summary, APPL1 Tg mice exhibit improved peripheral metabolism, reduced cardiac lipotoxicity, and improved insulin sensitivity. These cellular effects contribute to protection from HFD-induced cardiomyopathy.

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“…Adiponectin is a potent vasodilator and, similar to insulin, its vasodilatory effect is mediated via a NO-dependent mechanism (Cheng et al, 2007; Schmid et al, 2011; Xi et al, 2005). Inasmuch as adiponetin’s vasodilatory actions have been repeatedly demonstrated in conduit arteries and resistance arterioles (Cheng et al, 2007; Schmid et al, 2011; Xi et al, 2005), its effect on the microvasculature was unknown prior to our recent study published in Circulation Research(Zhao et al, 2013).…”

Section: Crosstalk Between Adiponectin and Insulin: The Microvascularmentioning

confidence: 99%

“…Unlike other adipokines, ample evidence from both laboratory animal and human studies has confirmed that adiponectin has an insulin-sensitizing action and its levels are decreased in animals or humans with obesity and insulin resistance (Arita et al, 1999; Berg et al, 2001; Combs et al, 2001; Fruebis et al, 2001; Hotta et al, 2000; Kadowaki et al, 2006; Weyer et al, 2001; Yamauchi et al, 2001). Furthermore, adiponectin exerts a beneficial effect on the cardiovascular system (Fesus et al, 2007) and hypoadiponectinemia is independently associated with endothelial dysfunction in both humans and animals (Cao et al, 2009; Iwashima et al, 2004; Kumada et al, 2003; Ouchi et al, 2003; Schmid et al, 2011; Tan et al, 2004; Torigoe et al, 2007). …”

Section: Introductionmentioning

confidence: 99%

Adiponectin and insulin cross talk: The microvascular connection

Zhao

Liu

2014

Trends in Cardiovascular Medicine

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Adiponectin exerts both vasodilatory and insulin-sensitizing actions and its levels are decreased in the insulin resistant humans and animals. The mechanisms underlying the adiponectin’s insulin-sensitizing effect have been extensively investigated but remain largely unclear. Muscle microvasculature critically regulates muscle insulin action by modulating insulin delivery to the microvessels nurturing the muscle cells and the trans-endothelial insulin transport. We have recently reported that adiponectin exerts its insulin-sensitizing effect via recruiting muscle microvasculature, expanding the endothelial surface area, and increasing insulin delivery to and thus action in muscle. The current review focuses on the microvascular connection between the adiponectin and insulin crosstalk.

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Globular and Full-Length Adiponectin Induce NO-Dependent Vasodilation in Resistance Arteries of Zucker Lean but Not Zucker Diabetic Fatty Rats

Cited by 44 publications

References 40 publications

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

APPL1 transgenic mice are protected from high-fat diet-induced cardiac dysfunction

Adiponectin and insulin cross talk: The microvascular connection

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