Novel mechanism of ghrelin therapy for cachexia

Hatanaka, Michiyoshi; Konishi, Masaaki; Ishida, Junnichi; Saito, Masakazu; Springer, Jochen

doi:10.1002/jcsm.12084

Cited by 12 publications

(7 citation statements)

References 10 publications

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“…87 Up-stream from the growth hormone/IGF-1 axis are several growth hormone secretagogues, of which ghrelin that is mainly produced in the fundus of the stomach has been studied extensively for the treatment of diseaserelated anorexia and conditions of muscle loss like sarcopenia and cachexia. Ghrelin has been shown to increase food intake in patients with cancer cachexia, 88,89 and anamorelin also improved muscle mass, but unfortunately not muscle strength. 90 Moreover, ghrelin prevented tumour-induced and cisplatin-induced muscle wasting in a mouse model of cancer cachexia.…”

Section: Sarcopenia In Heart Failurementioning

confidence: 99%

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

2017

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Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF‐1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one.

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Section: Sarcopenia In Heart Failurementioning

confidence: 99%

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

2017

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“…105 Ghrelin, which is primarily produced in the fundus of the stomach, has been used in disease-related anorexia and conditions of muscle loss like sarcopenia and cachexia. In cancer cachexia patients, ghrelin improves food intake, 106,107 possibly by modulation of the central control of appetite dysregulation during cancer anorexia. 63 The small Skeletal muscle wasting in chronic heart failure molecule ghrelin-analogue anamorelin also increased muscle mass but had no effect on muscle strength.…”

Section: Chronic Heart Failure and Muscle Maintenancementioning

confidence: 99%

Skeletal muscle wasting in chronic heart failure

2018

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Patients suffering from chronic heart failure (CHF) show an increased prevalence (~20% in elderly CHF patients) of loss of muscle mass and muscle function (i.e. sarcopenia) compared with healthy elderly people. Sarcopenia, which can also occur in obese patients, is considered a strong predictor of frailty, disability, and mortality in older persons and is present in 5–13% of elderly persons aged 60–70 years and up to 50% of all octogenarians. In a CHF study, sarcopenia was associated with lower strength, reduced peak oxygen consumption (peak VO2, 1173 ± 433 vs. 1622 ± 456 mL/min), and lower exercise time (7.7 ± 3.8 vs. 10.22 ± 3.0 min, both P < 0.001). Unfortunately, there are only very limited therapy options. Currently, the main intervention remains resistance exercise. Specialized nutritional support may aid the effects of resistance training. Testosterone has significant positive effects on muscle mass and function, and low endogenous testosterone has been described as an independent risk factor in CHF in a study with 618 men (hazard ratio 0.929, P = 0.042). However, the use of testosterone is controversial because of possible side effects. Selective androgen receptor modulators have been developed to overcome these side effects but are not yet available on the market. Further investigational drugs include growth hormone, insulin‐like growth factor 1, and several compounds that target the myostatin pathway. The continuing development of new treatment strategies and compounds for sarcopenia, muscle wasting regardless of CHF, and cardiac cachexia makes this a stimulating research area.

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“…The gastric hormone acylated ghrelin (AG) has orexigenic effects and complex metabolic activities that may include stimulation of SM mitochondrial oxidative capacity and insulin signalling in both healthy and diseased rodent models . Despite potential negative effects on circulating glucose reported in human and experimental models due to potential glucogenic activities, AG has been therefore extensively studied and increasingly suggested as potential anti‐catabolic treatment under chronic disease conditions associated with loss of body and muscle mass . We and others have shown beneficial effects of AG on body weight, muscle mass, and systemic inflammation in cancer and renal cachexia models .…”

Section: Introductionmentioning

confidence: 99%

Acylated ghrelin treatment normalizes skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rat chronic heart failure

Barazzoni

Cappellari

Palus

et al. 2017

J cachexia sarcopenia muscle

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BackgroundChronic heart failure (CHF) is associated with skeletal muscle abnormalities contributing to exercise intolerance, muscle loss, and negative impact on patient prognosis. A primary role has been proposed for mitochondrial dysfunction, which may be induced by systemic and tissue inflammation and further contribute to low insulin signalling. The acylated form of the gastric hormone ghrelin (AG) may improve mitochondrial oxidative capacity and insulin signalling in both healthy and diseased rodent models.MethodsWe investigated the impact of AG continuous subcutaneous administration (AG) by osmotic minipump (50 nmol/kg/day for 28 days) compared with placebo (P) on skeletal muscle mitochondrial enzyme activities, mitochondrial biogenesis regulators transcriptional expression and insulin signalling in a rodent post‐myocardial infarction CHF model.ResultsNo statistically significant differences (NS) were observed among the three group in cumulative food intake. Compared with sham‐operated, P had low mitochondrial enzyme activities, mitochondrial biogenesis regulators transcripts, and insulin signalling activation at AKT level (P < 0.05), associated with activating nuclear translocation of pro‐inflammatory transcription factor nuclear factor‐κB. AG completely normalized all alterations (P < 0.05 vs P, P = NS vs sham‐operated). Direct AG activities were strongly supported by in vitro C2C12 myotubes experiments showing AG‐dependent stimulation of mitochondrial enzyme activities. No changes in mitochondrial parameters and insulin signalling were observed in the liver in any group.ConclusionsSustained peripheral AG treatment with preserved food intake normalizes a CHF‐induced tissue‐specific cluster of skeletal muscle mitochondrial dysfunction, pro‐inflammatory changes, and reduced insulin signalling. AG is therefore a potential treatment for CHF‐associated muscle catabolic alterations, with potential positive impact on patient outcome.

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Novel mechanism of ghrelin therapy for cachexia

Cited by 12 publications

References 10 publications

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

Skeletal muscle wasting in chronic heart failure

Acylated ghrelin treatment normalizes skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rat chronic heart failure

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