Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure

Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Circulation (Impact Factor: 14.95). 12/2004; 110(24):3674-9. DOI: 10.1161/01.CIR.0000149746.62908.BB
Source: PubMed

ABSTRACT Ghrelin is a novel growth hormone-releasing peptide that also induces vasodilation, inhibits sympathetic nerve activity, and stimulates feeding through growth hormone-independent mechanisms. We investigated the effects of ghrelin on left ventricular (LV) function, exercise capacity, and muscle wasting in patients with chronic heart failure (CHF).
Human synthetic ghrelin (2 microg/kg twice a day) was intravenously administered to 10 patients with CHF for 3 weeks. Echocardiography, cardiopulmonary exercise testing, dual x-ray absorptiometry, and blood sampling were performed before and after ghrelin therapy. A single administration of ghrelin elicited a marked increase in serum GH (25-fold). Three-week administration of ghrelin resulted in a significant decrease in plasma norepinephrine (1132+/-188 to 655+/-134 pg/mL; P<0.001). Ghrelin increased LV ejection fraction (27+/-2% to 31+/-2%; P<0.05) in association with an increase in LV mass and a decrease in LV end-systolic volume. Treatment with ghrelin increased peak workload and peak oxygen consumption during exercise. Ghrelin improved muscle wasting, as indicated by increases in muscle strength and lean body mass. These parameters remained unchanged in 8 patients with CHF who did not receive ghrelin therapy.
These preliminary results suggest that repeated administration of ghrelin improves LV function, exercise capacity, and muscle wasting in patients with CHF.

Download full-text


Available from: Junji Moriya, Jun 22, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Stressful events in early life predispose to the development of eating disorders in adulthood. This study investigates how neonatal maternal separation (NMS) affects satiety and ghrelin secretion in adulthood. Methods. Sprague-Dawley rats underwent NMS and controls were without NMS. Experiments were conducted on day 60: (1) water avoidance stress (WAS); (2) feeding after overnight fasting; (3) feeding after overnight fasting and WAS. Blood samples, gastric and hypothalamic tissues expression were collected for ghrelin analysis. Results. (1) MS rats had a higher basal ghrelin. After WAS, MS rats had enhanced ghrelin. (2) A higher initial calorie intake and lower postprandial gastric ghrelin protein in MS are observed without difference in overall calorie intake. (3) MS had symptoms of binge eating and early satiation. Overall reduction of calorie intake was observed until 48 hours in MS. Conclusion. Stressful events in early life led to aberrant ghrelin profile and early satiation in response to stressful experience in adulthood.
    08/2012; 1(1):1-8. DOI:10.4303/ne/235603
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), shows cardioprotective activity and regulates the differentiation of several mesoderm-derived cells, including myocytes, adipocytes and osteoblasts. The effect of ghrelin on cardiogenesis and its underlying mechanism, however, have not been studied in detail. METHODS: The effects of ghrelin on cardiomyocyte differentiation were tested both in human embryonic stem cells (hESCs) cultured in embryoid body (EB)-based differentiation protocol, and in hESCs transplanted into rat hearts. The signaling mechanisms of ghrelin were further investigated under the EB-based culture condition. RESULTS: The generation of beating EBs and the expression of cardiac-specific markers including cardiac troponin I (cTnI) and α-myosin heavy chain (α-MHC) were 2 to 3-fold upregulated by ghrelin. Although GHS-R1α protein was expressed in differentiated EBs, the effects of exogenous ghrelin were unchanged by D-[lys(3)]-GHRP-6, a specific GHS-R1α antagonist. Moreover, des-acyl ghrelin, which does not bind to GHS-R1α, displayed similar effects with ghrelin. Importantly, activation of ERK1/2, but not Akt, was induced by ghrelin in the newly-formed EBs, and the ghrelin-induced effects of cardiomyocyte differentiation were abolished by adding specific ERK1/2 inhibitor PD98059, but not specific PI3K inhibitor Wortmannin. In addition, ghrelin promoted the differentiation of grafted hESCs into Sox9- and Flk1-positive mesodermal/cardiac progenitor cells in rat hearts. CONCLUSIONS: These results suggest that ghrelin induces cardiomyocyte differentiation from hESCs via the activation of the ERK1/2 signaling pathway. Our study, therefore, indicates that using ghrelin may be an effective strategy to promote the differentiation of hESCs into cardiomyocytes.
    International journal of cardiology 07/2012; 167(6). DOI:10.1016/j.ijcard.2012.06.106 · 6.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ghrelin, the natural ligand for the growth hormone (GH)-secretagogue receptor (GHS-R), is produced predominantly in the stomach. It is present in the circulation in two major forms, an acylated and an unacylated form, both of which have reported activities. Some of the best understood actions of acylated ghrelin administration are its orexigenic effects, and the stimulation of GH secretion. Ghrelin also seems to play a role in glucose homeostasis, lipid metabolism and immune function. Based on its orexigenic and metabolic effects, ghrelin and ghrelin mimetics have potential benefit in antagonizing protein breakdown and weight loss in catabolic conditions such as cancer cachexia, renal, cardiac and pulmonary disease, and age-related frailty. Ghrelin also has potentially useful positive effects on cardiac function and gastric motility. Ghrelin antagonists may be of benefit to increase insulin sensitivity and potentiate weight loss. The following chapter presents some background on ghrelin and ghrelin assays and discusses some of the potential therapeutic approaches for the use of ghrelin, ghrelin mimetic compounds and ghrelin antagonists in clinical disease.
    Molecular and Cellular Endocrinology 02/2011; 340(1):106-10. DOI:10.1016/j.mce.2011.02.010 · 4.24 Impact Factor