Lund LH, Williams JJ, Freda P, et al. 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: 6.53). 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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Available from: Lars H Lund, Sep 27, 2015
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    • "Increased plasma ghrelin levels during the progression of the HF induced by adriamycin may represent a compensatory selfprotective effect by improving cardiac function and retaining myocardial energy reserve [27]. Lund et al. also documented that plasma ghrelin in HF patients do not appear to depend on body mass index [28]. Maybe the elevated systemic ghrelin is a response to impaired cardiac ghrelin expression. "
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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 · 1.83 Impact Factor
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    • "Ghrelin agonists which mimic a natural ligand for the growth hormone secretagogue receptor stimulate food intake and appetite as well as having indirect ant-inflammatory effects via cytokines [52]. Ghrelin may play an important role in cachexia [53, 54] as perhaps does the less well-studied counter-balancing hormone, obestatin [55]. Studies underway are looking at ghrelin or analogues in the treatment of cachexia caused by chronic HF, chronic obstructive pulmonary disease [56], cancer and renal failure. "
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    ABSTRACT: Background The awareness of cardiac cachexia, i.e. involuntary weight loss in patients with underlying cardiovascular disease, has increased over the last two decades. Methods and results This mini-review looks at recent research in the cardiovascular literature that is relevant to the areas of interest of the Journal of Cachexia, Sarcopenia and Muscle. It identifies significant research in the last 3 years on the obesity paradox, the causes and effects of skeletal muscle wasting, animal models of cachexia and emerging treatment ideas in cardiac cachexia. Conclusions Assuming a similar literature in the fields of cancer, chronic obstructive pulmonary disease, chronic renal failure and chronic liver failure, the emergence of cachexia as a vibrant area of clinical and experimental research seems assured.
    11/2012; 3(4). DOI:10.1007/s13539-012-0090-6
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    • "Cross-sectional studies reveal an inverse correlation between circulating BNP and BMI not only in patients with heart failure, but also in healthy people (11). Heart failure is associated with resistance to the orexigenic hormone ghrelin (12), and ghrelin administration improves both left ventricular function and muscle wasting (13,14). "
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    ABSTRACT: Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.
    Diabetes 06/2012; 61(10):2592-6. DOI:10.2337/db11-1466 · 8.10 Impact Factor
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