Adiponectin, T-cadherin and Tumour Necrosis Factor-α in Damaged Cardiomyocytes from Autopsy Specimens

Takahashi, Takashi; Saegusa, Seiichiro; Sumino, Hiroyuki; Nakahashi, Takeshi; Iwai, Kunimitsu; Morimoto, Shigeto; Nojima, Takayuki; Kanda, Tsugiyasu

doi:10.1177/147323000503300212

Cited by 36 publications

(26 citation statements)

References 18 publications

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“…Therefore, adiponectin and TNFα may represent adipokines with important biological roles in cardiomyocytes. Recently, it was reported that adiponectin is localized at the periphery of damaged myocytes from myocardial and dilated cardiomyopathy patients [29]. Also, it has been shown that adiponectin treatment inhibits the progression of viral myocarditis through binding to the adiponectin receptor 1 in leptin-deficient mice [30].…”

Section: Discussionmentioning

confidence: 99%

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor γ

Ding¹,

Qin²,

He³

et al. 2007

Journal of Molecular and Cellular Cardiology

128

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Adiponectin is a protein hormone involved in maintaining energy homeostasis in metabolically active tissues. It enhances glucose and lipid metabolism via activation of AMP-dependent kinase (AMPK) in skeletal muscle and liver. Energy homeostasis is vital for the heart to work as a pump. In this study, we investigated whether adiponectin and its receptors are expressed in adult ventricular cardiomyocytes. We observed adiponectin transcript and protein in cultured ventricular cardiomyocytes isolated from adult rat, by quantitative real-time PCR, ELISA assays, Western blots, and immunofluorescent staining. In addition, we detected adiponectin receptor (AdipoR1 and AdipoR2) expression in the heart. AdipoR1 was expressed in rat myocardium at a level of about 50% of that in skeletal muscle; whereas adipoR2 was expressed at a similar level to that in liver. Rosiglitazone, a Peroxisome proliferator activated receptor γ (PPARγ) activator, substantially elevated expression of adiponectin in cultured cardiomyocytes and its secretion into cultured media. Rosiglitazone also increased adipoR1 and adipoR2 expression in cardiomyocytes. Treatment of recombinant globular adiponectin in cultured cardiomyocytes increased fatty acid oxidation and glucose uptake via activation of AMPK, suggesting a role for adiponectin in cardiac energy metabolism. Together, these data establish the existence of a local cardiac-specific adiponectin system that is regulated by PPARγ. Moreover, these findings indicate a role for adiponectin on normal myocardial energy homeostasis, in part, through the activation of AMPK.

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Section: Discussionmentioning

confidence: 99%

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor γ

Ding¹,

Qin²,

He³

et al. 2007

Journal of Molecular and Cellular Cardiology

128

View full text Add to dashboard Cite

show abstract

“…Adiponectin receptors are expressed by cardiac myocytes and heart tissues (Ivanov et al 2001, Lord et al 2005, Takahashi et al 2005, Yamauchi et al 2003, and recent studies have shown that adiponectin will modulate intracellular signaling and growth in these cells. In rat neonatal cardiac myocytes, adiponectin activates AMPK and inhibits both extracellular signalregulated kinase (ERK) activation and the hypertrophic response to α-adrenergic receptor stimulation (Shibata et al 2004a).…”

Section: Adiponectin and Hypertrophic Cardiomyopathymentioning

confidence: 99%

Cardioprotection by Adiponectin

Ouchi

Shibata

Walsh

2006

Trends in Cardiovascular Medicine

225

160

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Obesity-related disorders are closely associated with the pathogenesis of cardiovascular disease. Adiponectin is a circulating adipose tissue-derived hormone that is down-regulated in obese individuals. Hypoadiponectinemia has been identified as an independent risk factor for type 2 diabetes, coronary artery disease, and hypertension, and experimental studies show that adiponectin plays a protective role in the development of insulin resistance, atherosclerosis, and inflammation. More recent findings have shown that adiponectin directly affects signaling in myocardial cells and exerts beneficial actions on the heart after pressure overload and ischemia-reperfusion injury. This review focuses on the role of adiponectin in the regulation of myocardial remodeling and acute cardiac injury.

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“…It can also alleviate both alcoholic and nonalcoholic steatohepatitis and liver injuries induced by toxins such as carbon tetrachloride and lipopolysaccharides (17)(18)(19)(20). More recently, adiponectin has been proposed to play a protective role against cardiac hypertrophy and ischemia/reperfusioninduced myocardial infarction through the activation of AMP-activated protein kinase (AMPK) in myocardium (21)(22)(23).…”

mentioning

confidence: 99%

Post-translational Modifications of the Four Conserved Lysine Residues within the Collagenous Domain of Adiponectin Are Required for the Formation of Its High Molecular Weight Oligomeric Complex

Wang

Lam

Chan

et al. 2006

Journal of Biological Chemistry

227

180

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Adiponectin is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. However, the molecular basis that regulates the production of the adiponectin oligomers remains largely elusive. We have shown previously that several conserved lysine residues (positions 68 Here, we investigated the potential roles of these post-translational modifications in oligomeric complex formation of adiponectin. Gel filtration chromatography revealed that adiponectin produced from mammalian cells formed trimeric, hexameric, and high molecular weight (HMW) oligomeric complexes. These three oligomeric forms were differentially glycosylated, with the HMW oligomer having the highest carbohydrate content. Disruption of hydroxylation and glycosylation by substitution of the four conserved lysines with arginines selectively abrogated the intracellular assembly of the HMW oligomers in vitro as well as in vivo. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation were significantly decreased compared with healthy controls. Functional studies of adiponectin-null mice revealed that abrogation of lysine hydroxylation/glycosylation markedly decreased the ability of adiponectin to stimulate phosphorylation of AMP-activated protein kinase in liver tissue. Chronic treatment of db/db diabetic mice with wild-type adiponectin alleviated hyperglycemia, hypertriglyceridemia, hepatic steatosis, and insulin resistance, whereas full-length adiponectin without proper post-translational modifications and HMW oligomers showed substantially decreased activities. Taken together, these data suggest that hydroxylation and glycosylation of the lysine residues within the collagenous domain of adiponectin are critically involved in regulating the formation of its HMW oligomeric complex and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes.,Adiponectin, a hormone synthesized by adipocytes, is an abundant serum adipokine with potent insulin-sensitizing activity (1-3). Unlike most other adipokines, the plasma levels of adiponectin are significantly decreased in obese individuals and patients with insulin resistance, type 2 diabetes mellitus (T2DM), 2 and cardiovascular diseases (4 -7). Elevation of circulating adiponectin by either transgenic overexpression or direct supplementation with recombinant adiponectin can alleviate many metabolic abnormalities associated with various insulin-resistant and/or diabetic animal models (8 -12). The globular domain of adiponectin decreases postprandial blood glucose, enhances lipid clearance, and increases insulin sensitivity by enhancing fatty acid ␤-oxidation in skeletal muscle (8). On the other hand, full-length adiponectin generated from mammalian cells enhances the sensitivity of insulin to inhibit hepatic glucose production by suppressing the expression of several key enzymes involved in gluconeogenesis, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase (10).In addit...

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Adiponectin, T-cadherin and Tumour Necrosis Factor-α in Damaged Cardiomyocytes from Autopsy Specimens

Cited by 36 publications

References 18 publications

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor γ

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor γ

Cardioprotection by Adiponectin

Post-translational Modifications of the Four Conserved Lysine Residues within the Collagenous Domain of Adiponectin Are Required for the Formation of Its High Molecular Weight Oligomeric Complex

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