Elevated Circulating Level of Ghrelin in Cachexia Associated With Chronic Heart Failure

Abstract

Background-Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, that may also cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in the cachexia associated with chronic heart failure (CHF). Methods and Results-Plasma ghrelin was measured in 74 patients with CHF and 12 control subjects, together with potentially important anabolic and catabolic factors, such as GH and tumor necrosis factor (TNF-␣). Patients with CHF were divided into two groups, those with cachexia (nϭ28) and those without cachexia (nϭ46). Plasma ghrelin did not significantly differ between all CHF patients and controls (181Ϯ10 versus 140Ϯ14 fmol/mL, PϭNS). However, plasma ghrelin was significantly higher in CHF patients with cachexia than in those without cachexia (237Ϯ18 versus 147Ϯ10 fmol/mL, PϽ0.001). Circulating GH, TNF-␣, norepinephrine, and angiotensin II were also significantly higher in CHF patients with cachexia than in those without cachexia. Interestingly, plasma ghrelin correlated positively with GH (rϭ0.28, PϽ0.05) and TNF-␣ (rϭ0.31, PϽ0.05) and negatively with body mass index (rϭϪ0.35, PϽ0.01). Conclusions-Plasma ghrelin was elevated in cachectic patients with CHF, associated with increases in GH and TNF-␣ and a decrease in body mass index. Considering ghrelin-induced positive energy effects, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with CHF.

Association of genetic variants of ghrelin, leptin and UCP2 with malnutrition inflammation syndrome and survival in end-stage renal disease patients

“…Increased total ghrelin has been reported to be associated with cachexia in chronic heart failure patients (Nagaya et al 2001). Increased total ghrelin levels are also reported in dialysis patients (Perez-Fontan et al 2004).…”

Adipokines and ghrelin in gastric cancer cachexia

“…These findings support the presence of ghrelin resistance. It is also possible that ghrelin levels could increase to compensate for the increased metabolic rate and energy need, which was hypothesized by Nagaya et al [21] Several experimental studies have shown that ghrelin has an important role in the regulation of insulin via controlling pancreatic endocrine functions [22,23] . No significant relationship between ghrelin and insulin, fasting glucose level and HOMA-IR were found in the present study.…”

Ghrelin Gene Products in Acute and Chronic Inflammation

“…Ghrelin circulating concentrations are increased in pathological conditions characterized by cachexia, including chronic heart failure, COPD, and different types of cancer (Garcia et al 2005;Itoh et al 2004;Kerem et al 2008;Nagaya et al 2001;Shimizu et al 2003). Regardless of the underlying disease, this cachexiaassociated hyperghrelinemia may represent either a compensatory mechanism to the negative energy balance and the inflammatory state or the development of a resistance to the ghrelin signaling.…”

“…Ghrelin is commonly altered in pathological conditions affecting body mass and/or body energy metabolism, negatively correlating with body mass index (BMI) (van der Lely et al 2004). Ghrelin circulating levels are indeed lower in overweight or obese subjects than in normal individuals (Tschöp et al 2000), with the exception of Prader Willi syndrome (Cummings et al 2002), and higher in conditions characterized by energy inadequacy such as anorexia/cachexia associated with cancer (Garcia et al 2005;Shimizu et al 2003) and several other pathologies including chronic heart and renal failure, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (Cohen et al 2008;Itoh et al 2004;Nagaya et al 2001;Yoshimoto et al 2002). Insulin and glucose are among the major determinants of ghrelin secretion that, in turn, modulates insulin secretion and glucose metabolism (van der Lely et al 2004;Wiedmer et al 2007).…”