Early Changes in Ghrelin following Roux-en-Y Gastric Bypass: Influence of Vagal Nerve Functionality?

Background Roux-en-Y gastric bypass (RYGBP) effectively produces massive weight reduction, improving health in morbidly obese patients. The mechanisms for the weight loss, and the fate of the excluded gastric mucosa, are not fully clarified. To what extent the appetite-stimulating gastric peptide ghrelin is affected remains controversial. Methods Circulating concentrations of ghrelin, pancreatic polypeptide (PP), pepsinogen I (PGI) and gastrin were examined in 15 morbidly obese patients (median BMI 45 kg/m²) preoperatively, and on days 1, 2, 4, 6 and at months 1, 6 and 12 after RYGBP. Results Ghrelin levels fell on postoperative day 1 and increased after 1 month to preoperative levels, and rose further at 6 and 12 months. PP concentrations decreased on day 1 and subsequently returned to preoperative levels. PGI levels peaked transiently the first days after surgery and subsequently declined to lower than preoperative levels. Gastrin levels were gradually reduced postoperatively. Conclusion Ghrelin and PP fall transiently after surgery, possibly due to vagal dysfunction, and ultimately, as weight loss ensues, ghrelin secretion increases to higher than preoperative levels. The RYBGP procedure affects the gastric mucosa, as reflected by a transient increase in circulating PGI, and subsequently, the mucosa in the excluded stomach is at rest, as shown by low levels of PGI and gastrin.     

Timing of Meals and Exercise Affects Hormonal Control of Glucoregulation,Insulin Resistance,Substrate Metabolism,and Gastrointestinal Hormones,but Has Little Effect on Appetite in Postmenopausal Women

The current prevalence of obesity in the US is strongly associated with excessive food intake and insufficient physical activity. This study examined whether changing the timing of exercise before or after two daily meals could alter human appetite for food. Fifty-four healthy postmenopausal women were matched by body weight and assigned to two groups: (1) two bouts of 2-h moderate-intensity exercise ending one hour before each weight-maintenance meal (XM, n = 23), (2) two-hour moderate-intensity exercise starting 1 h after each weight-maintenance meal (MX, n = 23), and one sedentary control (SED) arm (n = 8). Measurements included appetite ratings, circulating glucose, free fatty acids (FFAs), a ketone body D-ß-hydroxybutyrate (BHB), glucoregulatory hormones insulin and glucagon, and gastrointestinal hormones associated with food digestion and absorption and implicated in appetite sensations. XM group increased concentrations of FFAs and BHB during exercise and increased insulin and homeostatic assessment of insulin resistance (HOMA-IR) during postprandial periods. MX group reduced postprandial insulin and HOMA-IR by about 50% without a major change in plasma glucose. There was brief suppression of hunger and an increase in satiation in both exercise groups near the end of the first postprandial period. The time course of hunger was unrelated to the perturbations in fuel metabolism, depletion of liver glycogen, and not correlated with concentration changes in hunger-stimulating hormone ghrelin during XM exercise before meals. Similarly, there was no correlation between the time course of fullness during exercise after meals with the postprandial secretion of gastrointestinal hormones including cholecystokinin (CCK) that has been linked to satiation. Hunger and satiation appear to depend on oral intake and gastrointestinal processing of nutrients and are not affected by metabolic and hormonal consequences of the timing of exercise with respect to meals. Moderate-intensity exercise performed shortly after meals induces a rapid and highly effective lowering of insulin resistance.     

Toward a consensus nomenclature for ghrelin,its non-acylated form,liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor

The stomach-derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward-related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non-acylated form of ghrelin, desacyl-ghrelin, can also be detected in biological samples. Desacyl-ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well-characterized than that of ghrelin. Ghrelin and desacyl-ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms “ghrelin” and “desacyl-ghrelin” to refer to the hormone itself and its non-acylated form, respectively. Based on the results of this consensus, we further propose using the terms “GHSR” for the receptor, and “LEAP2” for liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist.     

Differences in gastrointestinal hormones and appetite ratings between individuals with and without obesity—A systematic review and meta-analysis

Determining if gastrointestinal (GI) hormone response to food intake differs between individuals with, and without, obesity may improve our understanding of obesity pathophysiology. A systematic review and meta-analysis of studies assessing the concentrations of GI hormones, as well as appetite ratings, following a test meal, in individuals with and without obesity was undertaken. Systematic searches were conducted in the databases MEDLINE, Embase, Cochrane Library, PsycINFO, Web of Science, and ClinicalTrials.gov . A total of 7514 unique articles were retrieved, 115 included in the systematic review, and 70 in the meta-analysis. The meta-analysis compared estimated standardized mean difference in GI hormones' concentration, as well as appetite ratings, between individuals with and without obesity. Basal and postprandial total ghrelin concentrations were lower in individuals with obesity compared with controls, and this was reflected by lower postprandial hunger ratings in the former. Individuals with obesity had a lower postprandial concentration of total peptide YY compared with controls, but no significant differences were found for glucagon-like peptide 1, cholecystokinin, or other appetite ratings. A large methodological and statistical heterogeneity among studies was found. More comprehensive studies are needed to understand if the differences observed are a cause or a consequence of obesity.