Ghrelin resistance occurs in severe heart failure and resolves after heart transplantation.

Section for Heart Failure, Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
European Journal of Heart Failure (Impact Factor: 6.58). 06/2009; 11(8):789-94. DOI: 10.1093/eurjhf/hfp088
Source: PubMed

ABSTRACT Severe heart failure (HF) is often associated with cachexia that reverses post-heart transplantation (HTx) with frequent development of obesity. Ghrelin is a novel appetite-stimulating hormone. The aim was to determine the role of ghrelin in regulating appetite, food intake, and body composition in HF and post-HTx.
We measured serial ghrelin, hunger sensation, caloric intake, and body composition in 12 HF patients awaiting HTx, 12 patients 12.7 +/- 8.6 months post-HTx, and 7 controls. Seven of 12 HF patients were followed for longitudinal analysis post-HTx. Body mass index was 23.1 +/- 3.1 in HF and 31.5 +/- 5.5 post-HTx (P < 0.001). Heart transplantation patients had gained 18.0 +/- 7.7 kg since HTx. Ghrelin area under the curve between controlled meals (control: 186 +/- 39; HF: 264 +/- 71; HTx: 194 +/- 47 ng min/mL, P < 0.007) was higher in HF, but test meal caloric intake (control: 1185 +/- 650; HF: 391 +/- 103; HTx: 831 +/- 309 kcal, P < 0.008) was lower in HF. The longitudinal analysis confirmed these findings.
Heart failure may be associated with resistance to the appetite-stimulating effects of ghrelin, which may contribute to cachexia. Heart transplantation may be associated with resolution of ghrelin resistance, which may contribute to weight gain. These findings are preliminary and should be confirmed in larger trials.

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    ABSTRACT: ABSTRACT Objectives: Ghrelin is an anabolic hormone that is elevated in heart failure (HF), with resistance to its anabolic effects. This resolves after heart transplantation (HTx). Ghrelin exists in acylated and des-acyl forms, with primarily the acylated form responsible for endocrine actions. We tested the hypothesis that ghrelin derangements in HF are due to inadequate acylation and that this resolves post transplantation. Design: Plasma levels of des-acyl and acylated ghrelin and acylated/total ratios were assessed in HF (n=20), post-HTx (n=35) and healthy controls (n=4) and correlated with each other and with clinical parameters. Results: Des-acyl ghrelin (pg/ml), median (interquartile range), was 167 (121-195) in HF vs. 149 (130-223) post-HTx, p=NS. Acylated ghrelin was 76 (51-99) vs. 13, p<0.001. Acylated/total ratios were 0.33 (0.20-0.47) vs. 0.08 (0-0.13), p<0.001. The correlation between acylated and total ghrelin was greater in HF than HTx. Acyl ghrelin correlated inversely with body mass index in HF but not HTx. Conclusion: Acylated ghrelin and the acylated/total ratio were dramatically higher in HF compared to HTx. Acylation rather than secretion of ghrelin is upregulated in HF and the resistance to ghrelin's anabolic and appetite-stimulating effects is not at the level of acylation but down-stream at the ghrelin-receptor level.
    Scandinavian cardiovascular journal: SCJ 08/2014; DOI:10.3109/14017431.2014.955052 · 1.10 Impact Factor
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    ABSTRACT: Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on cardiac function and ventricular remodeling. The present study aimed to investigate the expression of ghrelin and the growth hormone (GH) secretagogue receptor 1a (GHSR-1a), and the association with cardiac remodeling in rats with myocardial infarction (MI). Twenty-four hours after ligation of the anterior descending artery (LAD), adult male Sprague-Dawley rats were randomized to 3 d, 7 d and 28 d group. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Expression of both ghrelin and GHSR-1a was assessed by means of immunohistochemistry and real-time PCR. Plasma ghrelin levels were measured by ELISA kit. In addition, cardiac remodeling was assessed by Echocardiographic and haemodynamic measurements. Plasma and cardiac expression of ghrelin decreased on days 3, 7 and 28 compared with the sham group (P < 0.05). In contrast the GHSR-1a mRNA levels increased during the same days (P < 0.05). Decreased positive immunoreaction for ghrelin and increased positive GHSR-1a was also observed in infarcted heart. Interestingly, plasma ghrelin correlated negatively with left ventricular end-diastolic pressure(r = -0.59, P = 0.002) and left ventricular end-diastloic dimension (r = -0.73, P < 0.01). The ghrelin system may play an important role regulating cardiac remodeling after MI and present as a potential significant target for pharmacological modulation and treating cardiac remodeling.
    Regulatory Peptides 06/2014; 192. DOI:10.1016/j.regpep.2014.07.001 · 2.01 Impact Factor
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    ABSTRACT: Muscle wasting is a comorbidity often associated with a wide range of disorders that severely affects patient prognosis and quality of life. Ghrelin, through its receptor GHSR-1a, stimulates appetite and growth hormone (GH) release. Several studies indicate that ghrelin administration is a valid treatment for cachexia because it improves muscle mass and function, likely by restoring a positive energy balance. In addition to its GHSR-1a-mediated effects on muscle mass, ghrelin acts directly on skeletal muscle, wherein it exerts a protective activity against muscle wasting. This direct activity is independent of GHSR-1a and is shared by the unacylated form of ghrelin, which does not bind GHSR-1a and is devoid of the effects on appetite and GH release. Both the acylated and unacylated forms of ghrelin might have therapeutic potential for the treatment of skeletal muscle wasting.
    02/2014; DOI:10.1097/MCO.0000000000000049

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