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Dependence of β3-adrenergic signaling on the adipokine leptin in cardiac myocytes

International Journal of Obesity volume 36, pages 876–879 (2012)Cite this article

Abstract

β3-Adrenergic receptors (β3ARs) negatively regulate β-adrenergic signaling via nitric oxide and are dependent on the adipokine leptin for normal expression in adipocytes, thus making β3AR an attractive candidate for cross-talk with leptin in the heart. Accordingly, we tested the hypothesis that cardiac β3AR expression and function are dependent on leptin and are severely diminished in leptin-deficient ob/ob mice. Using isolated cardiac myocyte physiology studies, we found that β3AR function was significantly diminished in ob/ob myocytes and in wild-type myocytes treated with leptin antagonist. This finding was supported by quantitative PCR demonstrating markedly decreased β3AR mRNA levels in ob/ob mice. Both β3AR mRNA and function were restored in ob/ob mice after in vivo leptin repletion. We propose that diminished β3AR signaling may be the critical element to explain the direct effects of leptin on the myocardium and suggest that this work reveals a key feature in the role of leptin in obesity-related cardiac hypertrophy and heart failure.

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References

  1. Barouch LA, Berkowitz DE, Harrison RW, O’Donnell CP, Hare JM . Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 2003; 108: 754–759.

    Article  CAS  Google Scholar 

  2. Barouch LA, Gao D, Chen L, Miller KL, Xu W, Phan AC et al. Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity. Circ Res 2006; 98: 119–124.

    Article  CAS  Google Scholar 

  3. Rozec B, Gauthier C . beta3-adrenoceptors in the cardiovascular system: putative roles in human pathologies. Pharmacol Ther 2006; 111: 652–673.

    Article  CAS  Google Scholar 

  4. Yang R, Barouch LA . Leptin signaling and obesity: cardiovascular consequences. Circ Res 2007; 101: 545–559.

    Article  CAS  Google Scholar 

  5. Collins S, Daniel KW, Rohlfs EM, Ramkumar V, Taylor IL, Gettys TW . Impaired expression and functional activity of the beta 3- and beta 1-adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice. Mol Endocrinol 1994; 8: 518–527.

    CAS  PubMed  Google Scholar 

  6. Breslow MJ, An Y, Berkowitz DE . Beta-3 adrenoceptor (beta-3AR) expression in leptin treated OB/OB mice. Life Sci 1997; 61: 59–64.

    Article  CAS  Google Scholar 

  7. Khan SA, Skaf MW, Harrison RW, Lee K, Minhas KM, Kumar A et al. Nitric oxide regulation of myocardial contractility and calcium cycling: independent impact of neuronal and endothelial nitric oxide synthases. Circ Res 2003; 92: 1322–1329.

    Article  CAS  Google Scholar 

  8. Arch JR . The discovery of drugs for obesity, the metabolic effects of leptin and variable receptor pharmacology: perspectives from beta3-adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol 2008; 378: 225–240.

    Article  CAS  Google Scholar 

  9. Moens AL, Yang R, Watts VL, Barouch LA . Beta 3-adrenoreceptor regulation of nitric oxide in the cardiovascular system. J Mol Cell Cardiol 2010; 48: 1088–1095.

    Article  CAS  Google Scholar 

  10. Moens AL, Leyton-Mange JS, Niu X, Yang R, Cingolani O, Arkenbout EK et al. Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor. J Mol Cell Cardiol 2009; 47: 576–585.

    Article  CAS  Google Scholar 

  11. Nickola MW, Wold LE, Colligan PB, Wang GJ, Samson WK, Ren J . Leptin attenuates cardiac contraction in rat ventricular myocytes. Role of NO. Hypertension 2000; 36: 501–505.

    Article  CAS  Google Scholar 

  12. Niu X, Leyton-Mange JS, Yang R, Cingolani O, Vandegaer K, Bedja D et al. Cardioprotective effect of beta-3 adrenoceptor agonism in pressure overload hypertrophy. J Am Coll Cardiol 2010; 55 (supplement A): A221.

    Google Scholar 

Download references

Acknowledgements

This study was supported by American Heart Association Beginning Grant-In-Aid 09BGIA2250379 (to LAB); American Diabetes Association 1-10-BS-11 Research Award (to LAB); NIH K08-HL076220 (to LAB); Max Kade-fellowship by the Austrian Academy of Sciences (to PPR); and NIH 5T32HL007227 (to VLW).

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    J E Larson, P P Rainer, V L Watts, R Yang, K L Miller, A Phan & L A Barouch

Authors
  1. J E Larson
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  2. P P Rainer
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  3. V L Watts
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  4. R Yang
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  5. K L Miller
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  6. A Phan
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  7. L A Barouch
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Correspondence to L A Barouch.

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The authors declare no conflict of interest.

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Larson, J., Rainer, P., Watts, V. et al. Dependence of β3-adrenergic signaling on the adipokine leptin in cardiac myocytes. Int J Obes 36, 876–879 (2012). https://doi.org/10.1038/ijo.2011.137

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  • DOI: https://doi.org/10.1038/ijo.2011.137

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