Rat heart is a site of leptin production and action

Purdham, Daniel M.; Zou, Min‐Xu; Rajapurohitam, Venkatesh; Karmazyn, Morris

doi:10.1152/ajpheart.00499.2004

Cited by 148 publications

(123 citation statements)

References 27 publications

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“…In this study, we utilized purified primary cardiomyocytes cultures being careful to exclude potential contamination by adipocytes to explore cardiac expression of adiponectin. Recently, a similar cardiac expression of leptin, another protein hormone that is involved in energy metabolic regulation, has been reported [26]. Adiponectin belongs to an adipokine superfamily.…”

Section: Discussionmentioning

confidence: 93%

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: 93%

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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“…The transcripts of three isoforms (ObRa, ObRb, and ObRe) of leptin receptor have been identified in the rat heart (26). ObRa is the short form of leptin receptor that lacks the intracellular signaling domain; its function is unclear (23).…”

Section: Discussionmentioning

confidence: 99%

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor

Lin

Huang

Hileman

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Leptin has been proposed to modulate cardiac electrical properties via ␤-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 g/kg) decreased resting heart rate; at high doses (150 -300 g/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 g/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of ␤-adrenergic receptor stimulation. During inhibition of ␤-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias.leptin; leptin receptor; resting heart rate; QT interval NEW & NOTEWORTHYLeptin is believed to increase heart rate via adrenergic receptor stimulation. We found evidence that leptin can exert local direct inhibition of heart rate and prolongation of QTc interval via its receptor. The findings offer better understanding of higher incidence of prolonged QT and sudden cardiac death in obesity.LEPTIN IS A 16-KDA ADIPOKINE released from adipocytes acting via its receptor. Detection of adipocytes in obese human heart (21, 30) and leptin receptors in human cardiac ventricles (19) has suggested that leptin can have autocrine and paracrine effects on cardiac functions.Leptin has been demonstrated to play an important role in cardiac contractility (19, 37), development of hypertrophy (12,19,37,39), and apoptosis (20). However, studies of leptin on cardiac electrical properties are rare and limited to indirect effects via adrenergic receptor stimulation. It has been widely accepted that leptin increases the heart rate through increasing sympathetic activity (5, 9, 10). Leptin-mediated increase in sympathetic activity can explain obese subjects with higher heart rate to meet the increased metabolic demands (25), but it cannot explain why many of them exhibit unchanged or decreased resting heart rate (2, 7).In heart failure patients, fatty infiltration of cardiomyocytes has been demonstrated. The percentage of fat in myocardium is positively correlat...

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“…The heart produces leptin itself, suggesting that it may act locally to mediate physiological effects (Purdham et al 2004, Karmazyn et al 2008. The primary cardiac physiological response to leptin is a reduction in cardiac output.…”

Section: Leptinmentioning

confidence: 99%

Role of adipokines in cardiovascular disease

Mattu¹,

Randeva²

2012

Journal of Endocrinology

251

203

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The discovery of leptin in 1994 sparked dramatic new interest in the study of white adipose tissue. It is now recognised to be a metabolically active endocrine organ, producing important chemical messengers -adipokines and cytokines (adipocytokines). The search for new adipocytokines or adipokines gained added fervour with the prospect of the reconciliation between cardiovascular diseases (CVDs), obesity and metabolic syndrome. The role these new chemical messengers play in inflammation, satiety, metabolism and cardiac function has paved the way for new research and theories examining the effects they have on (in this case) CVD. Adipokines are involved in a 'good-bad', yin-yang homoeostatic balance whereby there are substantial benefits: cardioprotection, promoting endothelial function, angiogenesis and reducing hypertension, atherosclerosis and inflammation. The flip side may show contrasting, detrimental effects in aggravating these cardiac parameters.

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Rat heart is a site of leptin production and action

Cited by 148 publications

References 27 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

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor

Role of adipokines in cardiovascular disease

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