Royce Vincent

Eating Slowly Increases the Postprandial Response of the Anorexigenic Gut Hormones, Peptide YY and Glucagon-Like Peptide-1

CONTEXTnThe rate at which people eat has been suggested to be positively associated with obesity, although appetite and related gut hormones have not been measured. The objective of the study was to determine whether eating the same meal at varying speeds elicits different postprandial gut peptide responses.nnnDESIGN AND SETTINGnThis was a crossover study at a clinical research facility.nnnSTUDY PARTICIPANTSnSeventeen healthy adult male volunteers participated in the study.nnnINTERVENTIONnA test meal consisting of 300 ml ice cream (675 kcal) was consumed in random order on two different sessions by each subject: meal duration took either 5 or 30 min.nnnMAIN OUTCOME MEASURESnThe postprandial response of the orexigenic hormone ghrelin and the anorexigenic peptides peptide YY and glucagon-like peptide-1 over 210 min was assessed. Visual analog scales for the subjective feelings of hunger and fullness were completed throughout each session.nnnRESULTSnPeptide YY area under the curve (AUC) was higher after the 30-min meal than after the 5-min meal (mean +/- sem AUC 5 min meal: 4133 +/- 324, AUC 30 min meal: 5250 +/- 330 pmol/liter . min, P = 0.004), as was glucagon-like peptide-1 AUC (mean +/- sem AUC 5 min meal: 6219 +/- 256, AUC 30 min meal: 8794 +/- 656 pmol/liter . min, P = 0.001). There was a trend for higher visual analog scale fullness ratings immediately after the end of the 30-min meal compared with immediately after the 5-min meal. There were no differences in ghrelin response.nnnCONCLUSIONSnEating at a physiologically moderate pace leads to a more pronounced anorexigenic gut peptide response than eating very fast.

Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation.

Objective:We aimed to determine changes in crypt cell proliferation and glucagon-like peptide-2 (GLP-2) in rodents and man after Roux-en-Y gastric bypass (RYGB). Summary of Background Data:Roux-en-Y gastric bypass results in sustained weight loss and reduced appetite with only mild gastrointestinal side effects. Glucagon-like peptide-2 released from intestinal l-cells after nutrient intake stimulates intestinal crypt cell proliferation and mitigates the effects of gut injury. Methods:Wistar rats underwent either RYGB (n = 6) or sham procedure (n = 6) and plasma GLP-2, GLP-1, and gut hormone peptide YY (PYY) were measured after 23 days. Biopsies from the terminal ileum were stained using the antibody to Ki67, which detects cyclins and hence demonstrates cells in the S-phase of the cell cycle. The total number of cells, number of mitosis, and number of labeled cells per crypt were counted. Obese patients (n = 6) undergoing RYGB were evaluated following a 420 kcal meal preoperatively, and 1, 3, 6, 12, and 24 months later for responses in l-cell products such as GLP-2, GLP-1, total PYY, and PYY3–36. Results:Rat GLP-2 levels after RYGB were elevated 91% above sham animals (P = 0.02). At necropsy, mitotic rate (P < 0.001) and cells positive for the antibody Ki67 (P < 0.001) were increased, indicating crypt cell proliferation. Human GLP-2 after RYGB reached a peak at 6 months of 168% (P < 0.01) above preoperative values. Area under the curve for GLP-1 (P < 0.0001), total PYY (P < 0.01), and PYY3–36 (P < 0.05) responses increased progressively over 24 months. Conclusions:RYGB leads to increased GLP-2 and mucosal crypt cell proliferation. Other gut hormones from l-cells remain elevated for at least 2 years in humans. These findings may account for the restoration of the absorptive surface area of the gut, which limits malabsorption and contributes to the long-term weight loss after RYGB.

The satiety hormone peptide YY as a regulator of appetite

Obesity is a major cause of premature death in the UK, and may contribute to as many as 30u2009000 deaths a year in the UK. Although effective treatment for obesity is still awaited, many developments have occurred to improve our understanding of neuroendocrine regulation of food intake and weight gain, especially regarding the role of gut hormones. One such gut hormone is peptide tyrosine-tyrosine also known as PYY where Y depicts the abbreviation for tyrosine. PYY is a 36 amino acid hormone, first isolated from porcine intestine. PYY, along with few other gut hormones, has been suggested as a potential therapeutic agent for obesity. This review examines the relationship of PYY to appetite regulation, energy homeostasis and the relevant neuroendocrine feedback mechanism.

Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes

Introduction:Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM.Methods:Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM.Results:A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found.Conclusions:This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.

Supraphysiological doses of intravenous PYY3-36 cause nausea, but no additional reduction in food intake

Abstract Background Peptide YY (PYY3-36) infused to levels within the physiological range reduces appetite and food intake in humans without nausea. However, PYY3-36 has previously been shown to cause nausea at higher doses. Methods We studied the relationship of PYY3-36, nausea and food intake in six volunteers, using three different PYY3-36 preparations infused to achieve supraphysiological PYY plasma levels. Results Supraphysiological levels of PYY caused nausea in five subjects (P < 0.05). Although PYY3-36 increased satiety (P < 0.05) and reduced food intake (P < 0.05), no greater enhancement of satiety or inhibition of food intake was observed compared with previous reports. Conclusions This study cautions against the use of supraphysiological doses of PYY3-36 as it may increase nausea with no benefit in food reduction.

OP014 THE IMPACT OF DUODENAL-JEJUNAL EXCLUSION ON SATIETY HORMONES

arterialized-venous plasma by LC-MS/MS. Fat-free mass was assessed by Dual-energy X-ray Absorptiometry. Statistics were done using Student’s t-Test. Results: Total ARG and CIT production were not different between COPD patients and healthy controls. However, de novo ARG production was reduced in COPD (7.12±0.6 vs. 10.6±1.5mmol/kg FFM/h, p = 0.027) and lower values were also found for whole body NO synthesis (0.31±0.1 vs. 0.74±0.1mmol/kg FFM/h, p < 0.01). Conclusion: Compromised NO synthesis is associated with a reduced de novo ARG production in patients with stable COPD. This suggests that in order to upregulate whole body NO synthesis in COPD, higher dietary intake of ARG or its precursor CIT is necessary.