Adipokines and ghrelin in gastric cancer cachexia

Kerem, Mustafa; Ferahköşe, Zafer; Yılmaz, Utku; Paşaoğlu, Hatîce; Ofluoglu, Ebru; Bedirli, Abdülkadir; Salman, Bülent; Sahin, Tevfik Tolga; Akın, Murat

doi:10.3748/wjg.14.3633

Cited by 85 publications

(76 citation statements)

References 30 publications

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“…[1][2][3] Moreover, it is not certain that whole-body fat retention depends preferentially on increased food intake after ghrelin administration. It may depend on the direct effects of ghrelin on metabolism in regional fat depots 31,44,45 or on other, unrecognized effects on cachexia. Estimations of calculated resting energy balance also supported a trend toward significantly improved energy balance over 8 weeks of treatment in patients who received high-dose ghrelin (P < .07), and the patients who received high-dose ghrelin were in energy balance (P < .05).…”

Section: Discussionmentioning

confidence: 99%

Effects by daily long term provision of ghrelin to unselected weight‐losing cancer patients

Lundholm

Gunnebo

Körner

et al. 2010

Cancer

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BACKGROUND:The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. METHODS: Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 lg/kg daily; n ¼ 17 patients) or low-dose ghrelin treatment (0.7 lg/kg daily; n ¼ 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. RESULTS: Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen,. CONCLUSIONS: The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism.

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Section: Discussionmentioning

confidence: 99%

Effects by daily long term provision of ghrelin to unselected weight‐losing cancer patients

Lundholm

Gunnebo

Körner

et al. 2010

Cancer

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“…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.…”

Section: Cachexiamentioning

confidence: 99%

Ghrelin Gene Products in Acute and Chronic Inflammation

Prodam,

Filigheddu

2014

Arch. Immunol. Ther. Exp.

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Ghrelin gene products-the peptides ghrelin, unacylated ghrelin, and obestatin-have several actions on the immune system, opening new perspectives within neuroendocrinology, metabolism and inflammation. The aim of this review is to summarize the available evidence regarding the less known role of these peptides in the machinery of inflammation and autoimmunity, outlining some of their most promising therapeutic applications.

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“…With respect to feeding behavior, a dose of ghrelin that stimulates FI results in circulating ghrelin levels similar to those detected after a 24 h fast [59]. Ghrelin receptor is expressed in the hypothalamus, and peripheral administration of ghrelin activates hypothalamic neuropeptide Y (NPY)/Y1 and agouti-related peptide (AgRP) pathways [60][61][62]. In addition, ghrelin induces FI via the orexin pathway [63].…”

Section: Homeostatic Regulatory Systemmentioning

confidence: 99%

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system [Review]

Ariyasu

Akamizu

2015

Endocr J

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Abstract. Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R or ghrelin receptor), is a 28-amino acid acylated peptide mainly produced in the stomach. The pharmacological administration of ghrelin is known to exert diverse effects, such as stimulating GH secretion, promoting food intake, and increasing adiposity. In recent years, genetically engineered mouse models have provided important insights into the physiology of various hormones. In this review, we discuss current knowledge regarding the physiological significance of ghrelin on the basis of studies using genetically engineered mouse models with modifications in the ghrelin system. Key word: GhrelinGHRELIN, an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R or ghrelin receptor), is a 28-amino acid acylated peptide [1]. Acyl-modification of ghrelin is essential for binding to ghrelin receptor, and is mediated by the membrane-bound ghrelin O-acyltransferase (GOAT) [2,3]. Ghrelin is mainly produced in the stomach, but is also expressed in the upper intestinal tract, pancreas, pituitary, and hypothalamus [1,4,5]. By contrast, the ghrelin receptor is expressed in the anterior pituitary and hypothalamus, suggesting that ghrelin/GHS-R signaling is involved in energy homeostasis and GH release [6][7][8]. Indeed, peripheral administration of ghrelin induces multiple effects, such as stimulating GH secretion, promoting food intake, and increasing adiposity [1,[9][10][11][12]. Using more sensitive PCR techniques, expression of ghrelin receptor has also been identified in the stomach, small intestine, pancreas, ventricular myocardium, aorta, adipose tissue, and lymphocytes [13][14][15]. The wide distribution of ghrelin and its receptor suggests that ghrelin might play a range of physiological roles.In order to investigate the physiological significance of hormones, genetically engineered mouse models have been widely utilized, and these models are also used as preclinical tools for exploring the novel therapeutic approaches for human disease. In this review, we discuss an outline of the physiological roles of ghrelin on the basis of research using genetically engineered mouse models, such as ghrelin-null, ghrelin receptor-null, ghrelin o-acyltransferase-null, and ghrelin-overexpressing mice. Secretion of GhrelinDate et al. reported that ghrelin-producing cells are X/A-like cells that account for about 20% of the endocrine cell population in rat and human oxyntic glands [16,17]. Ghrelin mRNA is most abundant in the stomach, and plasma ghrelin levels in totally gastrectomized patients were reduced to 35% of those in normal subjects, indicating that the stomach is a major source of circulating ghrelin [4]. Earlier studies revealed that circulating ghrelin levels reflect both acute and chronic energy status. In the acute phase, plasma ghrelin levels increase before meal and decrease after meal [4,[18][19][20]. In the chronic phase, plasma ghrelin levels are negatively correlated with BMI; for example, they ar...

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Adipokines and ghrelin in gastric cancer cachexia

Cited by 85 publications

References 30 publications

Effects by daily long term provision of ghrelin to unselected weight‐losing cancer patients

Effects by daily long term provision of ghrelin to unselected weight‐losing cancer patients

Ghrelin Gene Products in Acute and Chronic Inflammation

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system [Review]

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