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.     

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.     

肝硬化患者胃黏膜ghrelin表达及其临床意义

研究肝硬化患者胃黏膜ghrelin表达及其意义.选择肝硬化患者36例和内镜下胃黏膜大致正常者15例为对照组,测定肱三头肌皮褶厚度(triceps skinfold thickness,TSF)、血糖、胰岛素,进行食欲评价.肝硬化组胃黏膜表达ghrelin阳性细胞面积显著高于对照组(P＜0.001),且随着Child-Pugh分级增高有递增趋势.肝硬化组空腹血糖、胰岛素均显著高于对照组(P＜0.001,P＜0.05);胰岛素敏感指数(insulin sensitivity index,ISI)显著低于对照组(P＜0.05).肝硬化组ghrelin阳性细胞面积与食欲(r=-0.432)、TSF(r=-0.525)、ISI(r=-0.509)呈负相关(P＜0.05),与血糖(r=0.449)呈正相关(P＜0.05).肝硬化时ghrelin表达增高是机体对能量负平衡状态的一种适应性反应.胃黏膜ghrelin高表达可能参与了肝硬化患者的胰岛素抵抗作用.     

ghreIin在大鼠急性坏死性胰腺炎肺损伤中的作用及机制

目的探讨ghrelin在大鼠急性坏死性胰腺炎肺损伤中的作用和机制。方法 54只SD大鼠随机分为假手术（SO）组、急性坏死性胰腺炎（ANP）组和ghrelin干预组,采用胰胆管逆行注射5%牛磺胆酸钠诱导大鼠ANP模型,ghrelin干预组于模型制作前30 min和造模后3 h腹腔注射ghrelin,SO组开腹后翻动胰腺后关腹。观察各组大鼠血清淀粉酶的变化,ELISA检测血清肿瘤坏死因子-α（TNF-α）,光镜观察胰腺和肺组织的病理改变,Western blot检测肺组织核因子-κB（NF-κB）蛋白的表达,酶化学法测定肺组织髓过氧化物酶（MPO）的变化。结果 ANP组大鼠胰腺和肺组织随着时间延长病变加重;ANP组血清淀粉酶、TNF-α、肺组织MPO均较SO组明显升高（均P〈0.05）,表达水平与肺病理严重程度成正相关。ghrelin干预组各检测指标均较ANP组明显降低（均P〈0.05）,胰腺及肺组织病理损伤明显减轻。结论 ghrelin可减轻大鼠ANP后的肺损伤,并对MPO和TNF-α有明显的抑制作用,其机制可能与影响了NF-κB的表达,从而干预了炎症信号传导过程有关。     

二甲双胍对肥胖大鼠血清及下丘脑中胃促生长素表达的影响

目的观察肥胖大鼠血清及下丘脑中胃促生长素水平在二甲双胍干预前后的变化,探讨其在肥胖及代谢紊乱中的作用。方法 SD大鼠50只随机分为普通饮食(NC,n=10)组和高脂(n=40)组,16周高脂组成功建立肥胖模型后(n=20)随机分为:肥胖对照(OB)组,二甲双胍(MET)组,各10只。MET组灌胃MET 200 mg/(kg.d),OB组及NC组灌胃等剂量蒸馏水。分别测定干预前及干预6周后各组体重(BW)、空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TCH)、空腹胰岛素(FINS)、胰岛素抵抗指(HOMA-IR)及胃促生长素。免疫组化法检测各组大鼠下丘脑中胃促生长素表达水平。结果①干预前,OB组、MET组较NC组BW、FPG、TG、TCH、FINS、HOMA-IR升高,胃促生长素降低(P<0.05,P<0.01),OB组、MET组间各指标比较差异无统计学意义。MET干预后,MET组较OB组BW、TG、TCH、FPG、FINS、HOMA-IR降低,胃促生长素水平升高(P<0.05,P<0.01)。②免疫组化显示:OB组下丘脑中胃促生长素表达较NC组降低,MET组较OB组升高,差异有统计学意义(P<0.05,P<0.01)。③研究总体中FINS与胃促生长素呈负相关(r=-0.817,P<0.05)。结论肥胖大鼠血清及下丘脑胃促生长素水平降低,MET可改善胰岛素敏感性、降低BW,可能与血清及下丘脑胃促生长素水平增高有关。     

正加速度下实验性胃溃疡大鼠血清生长素和生长抑素的变化及机制

目的：探讨正加速度对慢性胃溃疡大鼠血清生长素（ghrelin）及生长抑素（somatostatin,SS）的变化及作用机制。方法雄性SD大鼠24只,建立乙酸致大鼠慢性胃溃疡模型,造模后随机分为对照组、＋5 Gz组和＋10 Gz组,每组8只。3 d后模拟不同＋Gz值正加速度条件,隔日1次,共4次,持续7 d。实验结束次日取大鼠胃黏膜及血液标本,HE染色病理切片,放射免疫法检测血清生长和生长抑素。结果在光镜下随＋Gz值增高,胃黏膜腺体形态异常,排列紊乱,炎性细胞浸润明显。各＋Gz值暴露组胃黏膜前列腺素E2（prostaglandin E2,PGE2）含量：＋10 Gz组为3.438±0.908 pg/ml,＋5 Gz组为5.147±0.652 pg/ml,对照组为6.986＆#177;0.743 pg/ml,＋10 Gz组低于＋5 Gz组（P＜0.05）,＋5 Gz组低于对照组（P＜0.05）。各＋Gz值暴露组血清生长素含量：＋10 Gz组为（94.48±23.96） ng/ml,＋5 Gz组为（142.56±38.63） ng/ml,对照组为（112.00±42.28） ng/ml,3组间差异有统计学意义（P＜0.05）,＋10 Gz组明显低于对照组（P＜0.05）,＋5 Gz组与对照组差异无统计学意义（P＞0.05）。各＋Gz值暴露组血清SS含量：＋10 Gz组（32.65±11.68） pg/ml,＋5 Gz组为（51.52±10.88） pg/ml,对照组为（38.37±14.16） pg/ml,3组间差异有统计学意义（P＜0.05）,＋5 Gz组明显高于对照组（P＜0.05）,＋10 Gz组与对照组差异无统计学意义（P＞0.05）。结论随＋Gz值增高,溃疡愈合质量下降;在中＋Gz值条件下血清SS升高,在高＋Gz值条件下血清生长素含量下降。     

ghrelin在能量代谢中的研究进展

新近研究发现,内源性生长激素促分泌素ghrelin在能量代谢中发挥重要调节作用,寻求ghrelin与糖尿病及相关内分泌激素关系的研究已成为探索2型糖尿病（T2DM）发病新的切入点。本文结合相关文献对ghrelin在能量代谢方面的研究进展综述如下。     

Circulating ghrelin was negatively correlated with pulmonary arterial pressure in atrial septal defect patients

Background Ghrelin was found to attenuate the magnitude of pulmonary arterial hypertension and pulmonary vascular remodeling in rats. The objective of this study was to explore the fasting plasma ghrelin level and the relationships between ghrelin and pulmonary arterial pressure （PAP） in atrial septal defect （ASD） patients with pulmonary arterial hypertension （PAH）,     

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.