Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an experimental study of conscious dogs

Ghrelin is a peptide that was discovered in endocrine cells of the stomach. However, its action in regulating the fasted and fed motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of an intravenous (i.v.) injection of canine ghrelin on the physiological fasted and fed motor activities in the stomach, duodenum, jejunum and colon of freely moving conscious dogs. An i.v. injection of canine ghrelin released growth hormone in a dose-dependent manner; however, it did not stimulate the motor activity of the digestive tract in either the fasted or the fed state. Moreover, an i.v. injection of high-dose canine ghrelin significantly reduced the motility index in the gastric body in the fasted state. Ghrelin did not accelerate gastric emptying, either. These results differ from previous reports dealing with rodents. It is significant that such results were obtained in research with dogs, which are larger animals.     

Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy—the two most commonly performed bariatric procedures—and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9–39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.     

Ghrelin after chemotherapy as a prognostic predictor of progression-free survival in patients with muscle-invasive bladder cancer

BackgroundAlthough the patients with muscle-invasive bladder cancer (MIBC) generally have poor prognosis, the utility of these biomarkers for the prediction of oncological outcomes in MIBC has not been completely explored. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, and angiogenesis. Thus, we aimed to evaluate the impact of serum ghrelin levels on survival in MIBC.MethodsIn this study, we reviewed the clinical and pathological records of 56 patients who were diagnosed with MIBC between November 2015 and November 2019 at Gifu and Hirosaki University Hospitals. We focused on 27 patients who had received chemotherapy and collected blood samples before and after chemotherapy. Blood samples were collected before chemotherapy and after completing two cycles of chemotherapy. Serum acyl (AG) and desacyl ghrelin (DG) were measured using AG and DG enzyme-linked immunosorbent assay kits (SCETI, Tokyo, Japan), respectively.ResultsThe 3-year overall and progression-free survival (PFS) rates were 82.9% and 68.3%, respectively. According to the AG level after chemotherapy, the 3-year PFS rates were 77.5% and 53.0% in patients with AG levels ≥1.34 and <1.34 pg/mL, respectively (P=0.038). With regard to DG levels after chemotherapy, the 3-year PFS rates were 90.9% and 43.3% in patients with DG levels <92.3 and ≥92.3 pg/mL, respectively (P=0.039). On multivariate analysis, serum AG levels were significantly associated with PFS.ConclusionsThis study suggested the usefulness of the ghrelin as a prognostic predictor of PFS in patients with MIBC.     

Growth hormone secretagogue receptor antagonists as potential therapeutic agents for obesity

Safe and efficacious medicines for obesity treatment are greatly needed. As an endogenous ligand of growth hormone secretagogue receptor 1a (GHS‐R 1a), ghrelin is the only known circulating orexigen. Administration of ghrelin causes food intake and body weight increase in both rodents and humans, whereas inhibiting its actions by antibodies, peptide antagonists, and anti‐sense oligonucleotides leads to decreased food intake and weight loss. Recent progress in developing nonpeptidyl small molecule GHS‐R antagonists is reviewed in this article. Drug Dev. Res. 65:50–54, 2005. © 2005 Wiley‐Liss, Inc.     

Chronic Renal Failure Impacts the Expression of Ghrelin and Its Receptor in Hypothalamus and Hippocampus

Background/Aims: Ghrelin plays a central role in the regulation of gastrointestinal (GI) motility. This study aimed to investigate the expression of ghrelin and growth hormone secretagogue receptor (GHSR) in the central nervous system of rats with chronic renal failure (CRF). Methods: Sprague-Dawley rats (male, 180 ± 20 g, n = 24) were treated by 5/6 nephrectomy to construct CRF model. As their plasma creatinine concentration and blood urea nitrogen were maintained more than double the normal level for 2 weeks, they were killed for assessing the expression of ghrelin and GHSR in hypothalamus and hippocampus using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). The rats (male, 180 ± 20 g, n = 24) treated by Sham operation served as a control. One-way analysis of variance and Student–Newman–Keuls q test were used to analyze group difference and a p-value of <0.05 was considered as statistically significant. Results: Compared with the controls, the ghrelin and GHSR expression was obviously increased in the hippocampus (p < 0.05) but decreased in the hypothalamus of rats with CRF (p < 0.05). Conclusions: CRF was found to impact the expression of ghrelin and GHSR in hypothalamus and hippocampus. This might be associated with the CRF-induced GI motility dysfunction.     

血清胃饥饿素、脂肪因子与膝骨关节炎患者骨密度的相关性研究

目的探讨血清胃饥饿素、脂肪因子水平与膝骨关节炎(knee osteoarthritis)患者骨密度(bone mineral density,BMD)之间的相关性。方法本研究选取了164例有症状的膝骨关节炎患者和100位健康人群(对照组)。使用酶联免疫吸附试验(ELISA)测量受试者血清胃饥饿素、脂联素和抵抗素水平。通过双能X线吸收测定法(DXA)测量受试者全身、腰椎、髋部和股骨的BMD。结果膝骨关节炎受试者的全身、腰椎、髋关节、股骨的BMD水平低于对照组(P均<0.05);但脂联素及胃饥饿素水平明显高于对照组(P均<0.05);在单因素分析中,血清胃饥饿素水平与所测量各个部位的骨密度之间有显著的负相关性(P<0.05);脂联素与股骨干骨密度和总股骨骨密度呈显著负相关(P<0.05)。进一步调整年龄、性别、体质量指数(body mass index,BMI)和骨关节炎(osteoarthritis,OA)后,胃饥饿素水平与各个部位的骨密度之间仍然存在显著负相关(P<0.05);脂联素与股骨干、股骨的骨密度之间有显著的相关性(P<0.05)。而血清抵抗素与各部位骨密度在混杂因素调整前后未发现显著相关性。结论血清胃饥饿素和脂联素水平与BMD呈显著负相关,提示胃饥饿素和脂联素对膝骨关节炎患者BMD有潜在的不利影响。     

Cancer cachexia: drugs in the patent literature

Background: The therapeutic approach to the neoplastic patient with cachexia is very frustrating for the physician. Indeed, we can say that a cure for cancer cachexia does not exist. Numerous therapeutic strategies have been tested in the last few decades with discouraging or at least conflicting results. Methods: Drugs patented for the treatment of cancer cachexia are evaluated and discussed. Results: New drugs such as ghrelin splice variant, small-molecule melanocortin-4 receptor antagonists and selective androgen receptor modulators have been discovered, evaluated with promising results, and patented. It is expected that soon they will be tested in humans through adequate clinical trials in experimental studies. Other compounds such as retinoid X receptor agonists, the inhibitor of LPS-induced TNF-α factor (LIPAF) protein, novel inhibitors of TNF-α production or release and tumour cytotoxic factor II need to be tested first in experimental models of cancer cachexia. Conclusion: With the recent discovery of new, effective drugs, it seems that a new scenario is opening up in the therapy of cancer cachexia.