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Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.

ABSTRACT: Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer.

SUBMITTER: Sever S

PROVIDER: S-EPMC5064755 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.

Sever Sakine S White Donna L DL Garcia José M JM

Endocrine-related cancer 20160901 9

Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review ...[more]

PMID: 27552970

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Project description:BackgroundGhrelin is a gut hormone with numerous physiological effects, including the regulation of energy balance, insulin sensitivity, vascular health, and body composition. Acylated (AG) and des-acylated (DAG) ghrelin constitute approximately 22 % and 78 % of total plasma ghrelin (TG), respectively. Alterations in the TG concentration and the AG/DAG ratio may be implicated in conditions involving energy imbalances and insulin resistant states (e.g., metabolic syndrome or Type 2 diabetes mellitus). Exercise is a therapeutic option that can potentially optimize ghrelin levels. Understanding the precise intensity and dose of exercise to optimize ghrelin levels may lead to targeted interventions to restore metabolic regulation in obesity and other clinical conditions.ObjectiveTo perform a systematic review and meta-analysis on the effects of acute exercise on pre-prandial levels of TG, AG, and DAG in healthy adults and to determine if sample demographics or exercise doses moderate such effects.MethodsElectronic databases (PubMed, Medline, SPORTDiscus, Web of Science, and Google Scholar) were searched with articles published through August 2020. The following criteria was determined a priori for article inclusion: (i) the study was a randomized controlled trial (RCT),(ii) exercise was an acute bout, (iii) the exercise bout for the intervention group(s)/condition was structured, (iv) the control group/condition received no exercise, (v) participants were adults age 18 or older, (vi) ghrelin was sampled through blood, (vii) there was at least one baseline measure and one post-exercise measure of ghrelin, (viii) there were at least 3 timepoints where ghrelin was measured while participants were fasted to allow for pre-prandial total area-under-the-curve (AUCtotal) calculation, (ix) participants were healthy with no overt disease, (x) interventions were carried out without any environmental manipulations. Standardized mean difference (SMD) with 95 % confidence intervals were calculated using the restricted maximum likelihood estimation Moderator analyses to determine whether the overall pooled effect was influenced by: sex, ghrelin form, method of ghrelin analysis, age, body mass index, body fat percentage, fitness, intensity of exercise bout, duration of exercise bout, energy expenditure, and length of AUCtotal data.ResultsThe analysis included 24 studies that consisted of 52 trials, n = 504 (age 27.0 (8.8) years, BMI 24.7 (2.7) kg/m2) and measured AG (n = 38 trials), DAG (n = 7), and TG (n = 7). The overall model indicated that exercise lowered ghrelin levels compared to control (no exercise); (SMD=-0.44, p < 0.001), and exercise intensity exhibited an inverse relationship with ghrelin levels (regression coefficient (ß)=-0.016, p = 0.04). There was no significant difference by ghrelin form (p = 0.18).DiscussionAcute exercise significantly lowers plasma ghrelin levels, with higher intensity exercise associated with greater ghrelin suppression. The majority of studies applied a moderate intensity exercise bout and measured AG, with limited data on DAG. This exercise dose may be clinically significant in individuals with metabolic dysregulation and energy imbalance as a therapy to optimize AG levels. More work is needed to compare moderate and high intensity exercise and the ghrelin response in clinical populations.

Project description:BackgroundHeart failure (HF) continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF.MethodsData sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014) which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration) on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE's risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3.ResultsA total of 325 animals (rats and mice) were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47) i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more) as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66) while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48) and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02) were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29) and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6.82, P=0.59).ConclusionsThe existing data provides evidence to suggest that Ghrelin may lower the risk of mortality and improve cardiovascular outcomes. However; the quality of evidence as assessed by GRADEpro is low to very low. Clinical judgments to administer Ghrelin to patients with HF must be made on better designed animal studies.

Project description:BackgroundAdolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis.MethodsWe conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI).ResultsSeven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of - 0.95 (95% CI - 1.43 to - 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively.ConclusionOur current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.

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Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.

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Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.

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