Commentary on the effects of ghrelin on the body weight, body composition, and cardiovascular function in experimental rat models of heart failure: A systematic review

How to cite this article:
Yang P. Commentary on the effects of ghrelin on the body weight, body composition, and cardiovascular function in experimental rat models of heart failure: A systematic review. Ann Trop Med Public Health 2015;8:81-2


How to cite this URL:
Yang P. Commentary on the effects of ghrelin on the body weight, body composition, and cardiovascular function in experimental rat models of heart failure: A systematic review. Ann Trop Med Public Health [serial online] 2015 [cited 2015 Sep 13];8:81-2. Available from:

The growth hormone-releasing peptide ghrelin is a polypeptide of 28 amino acid residues discovered by Kojima et al. in 1999. It is an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and has several biological functions, including growth hormone-releasing powers and a potent orexigenic action. In addition, the beneficial effects of ghrelin in cardiovascular diseases have been recently suggested. In humans as well as animals, the administration of ghrelin improves cardiac function, decreases inotropic and lusitropic effects, improves endothelial function, inhibits cardiomyocyte apoptosis, and ameliorates remodeling in chronic heart failure. In-depth understanding of the physiological role of ghrelin and its relationship with heart failure has great significance for clinical applications.

People have done a lot of research on the relationship between ghrelin and heart failure, but the exact effects of ghrelin on the cardiovascular system are inconclusive at present. Furthermore, although it has good prospects in the treatment of heart failure, the optimal dosage, route, and schedule of ghrelin are not clear yet. Since most of the researches on the relationship of ghrelin and chronic heart failure use rats as the disease model, the systematic review was done to determine the effectiveness of ghrelin therapy on weight gain and cardiovascular outcomes in experimental rat models of chronic heart failure. [1]

All publications describing controlled trials, systematic reviews, meta-analyses, and review papers published within 1999-2013 of ghrelin in animal models of heart failure were screened and finally five trials were elected, with the total sample size of 382 rats randomly divided into ghrelin-treated groups and nontreated groups. Reported outcomes included mortality, food intake, weight gain, cardiac effects, and hemodynamic and hormonal effects, and finally the author reached the conclusion that ghrelin apparently offered an effective therapeutic target for improving the outcome in experimental models of heart failure and thus, warranted further research. Moreover, the review evaluated optimal dosage, route, and schedule, and came up with the points that chronic subcutaneous administration of ghrelin improved left ventricular (LV) dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with congestive heart failure (CHF). Ghrelin, as low as 1 nmol/kg/d, significantly attenuated myocardial injury.

Only five trials were included in the review and the sample size was limited. In addition, each trial had different purposes and emphasized differently, so the conclusions have certain limitations; however, these still have significance to provide a direction for further research and ideas. Apart from this, all the subjects included in the review were male rats; gender difference in chronic heart failure and in drug effects was neglected, so further study is necessary to evaluate the effects of ghrelin on female rats.

The relationship of ghrelin and chronic heart failure was discussed in the review, but the effects of ghrelin on CHF and the mechanisms were unclear. Although how ghrelin may influence CHF is not fully understood, the cardiovascular beneficial effects are mediated possibly through a combination of various actions as follows:

  1. Ghrelin can inhibit angiotensin II (Ang II)-induced cardiomyocyte apoptosis by downregulating angiotensin II receptor type 1 (AT1R), thereby playing a role in preventing heart failure (HF), [2],[3]
  2. Ghrelin decreases the myocardial injury by downregulating inflammation factors such as tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β), [4]
  3. Ghrelin inhibits excessive activation of renin-angiotensin-aldosterone system through suppressing sympathetic nerve activity [5] and therefore, may have important therapeutic benefits in CHF,
  4. Ghrelin can attenuate cardiac dysfunction and energy metabolic disturbance in CHF in rats probably through regulating myocardial mitochondria function, [6] and
  5. Exogenous administration with ghrelin attenuates myocardial calcification induced by nicotine and vitamin D3. [7]

Nowadays, the relationship between ghrelin and cardiovascular diseases is a hot topic in research, especially the potent cardioprotective actions in CHF through various mechanisms. Since ghrelin is an endogenous hormone, it has advantages over other medications. The review analyzed and summarized the relationship between ghrelin and CHF, and finally gave a comprehensive conclusion that ghrelin can be a promising new treatment for CHF. I suggest that researches in people and in vitro should be analyzed so as to help us to fully understand the effects and mechanisms of ghrelin in CHF.



Khatib MN, Gode D, Simkhada P, Agho K, Gaidhane S, Saxena D, et al. Somatotropic and cardio-protective effects of ghrelin in experimental models of heart failure: A Systematic Review 2014;7:30-42.
Yang C, Liu Z, Liu K, Yang P. Mechanisms of ghrelin anti-heart failure: Inhibition of Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R expression. PLoS One 2014;9:e85785.
Yang C, Wang Y, Liu H, Li N, Sun Y, Liu Z, et al. Ghrelin protects h9c2 cardiomyocytes from angiotensin II-induced apoptosis through the endoplasmic reticulum stress pathway. J Cardiovasc Pharmacol 2012;59:465-71.
Huang CX, Yuan MJ, Huang H, Wu G, Liu Y, Yu SB, et al. Ghrelin inhibits post-infarct myocardial remodeling and improves cardiac function through anti-inflammation effect. Peptides 2009;30:2286-91.
Schwenke DO, Tokudome T, Kishimoto I, Horio T, Cragg PA, Shirai M, et al. One dose of ghrelin prevents the acute and sustained increase in cardiac sympathetic tone after myocardial infarction. Endocrinology 2012;153:2436-43.
Xu Z, Wu W, Zhang X, Liu G. Endogenous ghrelin increases in adriamycin-induced heart failure rats. J Endocrinol Invest 2007;30:117-25.
Wang F, Jiang T, Tang C, Su Z, Zhang N, Li G. Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo. Int J Mol Med 2011;28:513-9.

Source of Support: None, Conflict of Interest: None

Paul Mies has now been involved with test reports and comparing products for a decade. He is a highly sought-after specialist in these areas as well as in general health and nutrition advice. With this expertise and the team behind, they test, compare and report on all sought-after products on the Internet around the topics of health, slimming, beauty and more. The results are ultimately summarized and disclosed to readers.


Please enter your comment!
Please enter your name here