Plasma Peptide YY Levels Research Articles

Plasma Levels of Peptide YY in Obese Adolescents Throughout A Year of Treatment for Weight Loss

Objective: To evaluate serum PYY levels in obese adolescents treated in an outpatient obesity treatment program at a public hospital in southern Brazil. Methods: Fifty-one adolescents with obesity were included and followed up for 12 months. They attended 12 consultations with weight loss recommendations based on quantitative and qualitative food goals and reduction of sedentary behavior. Fasting serum levels of PYY, total cholesterol, HDL-cholesterol, triglycerides (TG), LDLcholesterol (LDL-C), insulin and glycemia were collected in T0 (before the first consultation), T1 (after 24 weeks) and T2 (after 48 weeks). Besides blood samples, abdominal circumference (AC) was measured, and the homeostasis model assessment (HOMA-IR) was calculated. By electrical bioimpedance analysis, fat mass and basal metabolic rate were measured. Results: Between T0 and T2, there was weight loss with a significant reduction of body mass index (BMI) Z-scores (p<0.001). There were also a significat reduction of PYY (p=0.026), TRIG (p=0.016), LDL-C (p=0.016), HOMAIR (p=0.004), AC (p<0.001) and BMI (p=0.002). In T2, there was a reduction in the baseline weight and in the proportion of severe obesity, and there was an increase in PYY levels (r=-0.421; p=0.002). Conclusion: Obese adolescents who changed their sedentary behavior and adopted a balanced diet showed weight loss and increse in PYY levels.

Peptide YY Causes Apathy-Like Behavior via the Dopamine D2 Receptor in Repeated Water-Immersed Mice

Apathy is observed across several neurological and psychiatric conditions; however, its pathogenesis remains unclear. We clarified the involvement of brain–gut signaling in the disruption of goal-directed behavior. Male C57BL/6J mice were exposed to water immersion (WI) stress for 3 days. Food intake and nesting behavior were measured as indexes of motivation. Repeated WI caused decrease in food intake and nesting behavior. Plasma levels of peptide YY (PYY), IL-6, and ratio of dopamine metabolites in the striatum were significantly elevated after WI. PYY and IL-6 administration significantly decreased nesting behavior. The reductions in feeding and nesting behavior were blocked by PYY receptor (Y2R) antagonist or dopamine agonist. The ameliorative effect of the Y2R antagonist was diminished by the dopamine D2 receptor (D2R) antagonist. The reduction in goal-directed behavior is associated with dysfunction of D2R signaling via increased peripheral PYY, suggesting that PYY antagonism is a novel candidate for decline of motivation in several depressive diseases.

Is There a Role for Enterohormones in the Gastroparesis of Critically Ill Patients?

Delayed gastric emptying occurs in critically ill patients and impairs the delivery, digestion, and absorption of enteral feeding. A pathophysiologic role of the enterohormones peptide YY and ghrelin is supported by preclinical data. To compare the circulating plasma levels of peptide YY and ghrelin in control subjects and in critically ill patients, during feeding and fasting, and to search for a correlation with gastric emptying. A prospective observational trial. Mixed ICU of an academic hospital. Healthy volunteers and patients expected to stay in ICU for at least 3 days in whom enteral nutrition was indicated. None. Plasma peptide YY and ghrelin (enzyme-linked immunosorbent assay) were measured once in 10 fasting volunteers (controls) and daily from admission until day 5 of the ICU stay in 30 critically ill patients (median [interquartile range] age 63 [57-67] yr, median [interquartile range] Acute Physiology and Chronic Health Evaluation II score 21 [14-24]). Eight patients could not be fed (fasting group). In fed patients, 13 never had a gastric residual volume higher than 250 mL (low gastric residual volume group), in contrast to the high gastric residual volume group (n = 9). The plasma levels of peptide YY did not differ between patients (6.4 [0-18.1] pg/mL) and controls (4.8 [0.3-17.7] pg/mL). Ghrelin levels were lower in patients than in control (213 [54.4-522.7] vs 1,435 [1,321.9-1,869.3] pg/mL; p < 0.05). Plasma peptide YY or ghrelin did not differ between fasting and fed patients or between the high and low gastric residual volume groups. In critically ill patients, plasma concentration of ghrelin significantly differs from that of controls, irrespective of the feeding status. No correlation was found between the temporal profile of ghrelin or peptide YY plasma concentration with bedside functional assessment of gastric emptying.

Fasting plasma peptide YY concentrations are increased in patients with major depression who associate weight loss.

Many patients with major depression refer a decreased appetite and weight loss among their symptoms. Peptide YY (PYY) and ghrelin belong to the family of peptides of the gut-brain axis implicated in the regulation of appetite and energy metabolism. PYY stimulates a powerful central satiety response and ghrelin increases food intake and weight gain. Brain-derived neurotrophic factor (BDNF) also contributes to the central control of food intake as an anorexigenic factor. To study fasting plasma total and acylated ghrelin, plasma PYY and serum BDNF levels in patients with major depression with weight loss as one of their symptoms and compare them with matched healthy controls. Fifteen adult patients, 9 male and 6 female, with recent diagnosis of major depression, and 16 healthy adult subjects, matched by age and anthropometric parameters were studied. All depressed patients referred weight loss and were not under antidepressant therapy. Fasting total PYY, total ghrelin and acylated ghrelin and BDNF were determined. Fasting total PYY was higher in patients than controls (2.01±0.09 vs 1.29±0.16 pmol/l). There were no differences in fasting total ghrelin, acylated ghrelin or BDNF levels. Major depressed patients, with weight loss at diagnosis, showed higher fasting plasma PYY levels that could contribute to their reduced appetite.

Plasma ghrelin and peptide YY levels in patients with type 2 diabetes before and after metformin treatment

Objective To investigate the effects of metformin on plasma ghrelin and peptide YY (PYY)levels in newly-diagnosed type 2 diabetic patients,and to study the impact of metformin on body weight.Methods A prospective nested case-control study was designed as a research protocol.Sixty four newly-diagnosed type 2 diabetic patients were treated with metformin for 12 weeks.The patients were divided into two groups:weight loss group and non-weight loss group according to the changes in body weight after metformin treatment.Fasting plasma ghrelin and PYY levels and other metabolic parameters were measured before and after metformin treatment.Results Fasting plasma ghrelin level was significantly decreased in the patients after metformin treatment [ ( 10.71 ±2.68 vs 11.81 ±3.19 )ng/ml,P＜0.05 ].Fasting plasma PYY level was significantly increased in patients after metformin treatment [ ( 136.86+39.14 vs 128.42+37.31 ) pg/ml,P＜0.05 ].After metformin treatment,43.7％ of the patients lost body weight significantly.Fasting plasma ghrelin level was decreased by 16.6％ after treatment in the weight loss group,as compared with 6.2％ in non weight loss group( P＜0.05 ).Fasting plasma PYY level was increased by 10.8％ after treatment in the weight loss group,as compared with 3.5％ in the non-weight loss group (P ＜ 0.05 ).Conclusions The fasting plasma ghrelin level in the weight loss group was lowered more significantly compared with that in the non-weight loss group after metformin treatment.The fasting plasma PYY level in the weight loss group was elevated more significantly as compared with that in the non-weight loss group after metformin treatment.The mechanism remains to be further studied. Key words: Metformin; Diabetes mellitus, type 2; Body mass index; Ghrelin; Peptide YY

The Gut Hormone Response Following Roux-en-Y Gastric Bypass: Cross-sectional and Prospective Study

Bariatric surgery is the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass. Although there is increasing interest in the gut hormone changes after gastric bypass, the long-term changes have not been fully elucidated. Thirty-four participants were studied cross-sectionally at four different time points, pre-operatively (n = 17) and 12 (n = 6), 18 (n = 5) and 24 months (n = 6) after laparoscopic Roux-en-Y gastric bypass. Another group of patients (n = 6) were studied prospectively (18-24 months). All participants were given a standard 400 kcal meal after a 12-h fast, and plasma levels of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were correlated with changes in appetite over 3 h using visual analogue scores. The post-operative groups at 12, 18 and 24 months had a higher post-prandial PYY response compared to pre-operative (p < 0.05). This finding was confirmed in the prospective study at 18 and 24 months. There was a trend for increasing GLP-1 response at 18 and 24 months, but this did not reach statistical significance (p = 0.189) in the prospective study. Satiety was significantly reduced in the post-operative groups at 12, 18 and 24 months compared to pre-operative levels (p < 0.05). Roux-en-Y gastric bypass causes an enhanced gut hormone response and increased satiety following a meal. This response is sustained over a 24-month period and may partly explain why weight loss is maintained.

Increases in peptide Y-Y levels following oat β-glucan ingestion are dose-dependent in overweight adults

Peptide Y-Y (PYY) is an anorexigenic hormone implicated in appetite control, and beta-glucan is a fiber known to affect appetite. We hypothesized that plasma PYY levels would increase in overweight human adults consuming increasing doses of beta-glucan. The objective was to test whether the effect could be seen with beta-glucan delivered through extruded cereals containing a high beta-glucan oat bran with demonstrated high molecular weight and solubility. Fourteen subjects consumed a control meal and 3 cereals of varying beta-glucan concentration (between 2.2 and 5.5 g), and blood samples were collected over 4 hours. Analysis of raw PYY data showed a trend toward significant increases over 4 hours. An increasing dose of beta-glucan resulted in higher levels of plasma PYY, with significant differences between groups from 2 to 4 hours post test-meal. Data for the area under the curve analysis also approached significance, with post hoc analysis showing a difference (P = .039) between the control and the highest dose of beta-glucan (5.5 g). The PYY levels at 4 hours were significantly different between the control and high-dose meal test (P = .036). There was a significant dose response, with a positive correlation between the grams of beta-glucan and PYY area under the curve (r(2) = 0.994, P = .003). The optimal dose of beta-glucan appears to lie between 4 and 6 g, with the effects on PYY mediated by viscosity and concentration. Meal-test studies examining a range of hormones should measure hormones over a minimum of 4 hours and record meal intake for even longer time frames.

Changes in gut hormone levels and negative energy balance during aerobic exercise in obese young males

We examined whether changes in gut hormone levels due to a single bout of aerobic exercise differ between obese young males and normal controls, and attempted to determine the involvement of hormonal changes during exercise in the regulation of energy balance (EB) in these obese subjects. Seven obese and seven age-matched subjects of normal weight participated in exercise and rest sessions. Subjects consumed a standardized breakfast that was followed by constant cycling exercise at 50% VO(2max) or rest for 60 min. At lunch, a test meal was presented, and energy intake (EI) and relative energy intake (REI) were calculated. Blood samples were obtained at 30 min intervals during both sessions for measurement of glucose, insulin, glucagon, ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise. The areas under the curve (AUC) of the time courses of PYY and GLP-1 levels did not significantly differ between the two groups. In contrast, EI and REI were decreased by exercise in both groups, and energy deficit was significantly larger in obese subjects than in normal controls. The present findings suggest that short-term EB during a single exercise session might be regulated not by increased amounts of these gut hormones per se.

Changes of the Peptide YY Levels in the Intestinal Tissue of Rats with Experimental Colitis following Oral Administration of Mesalazine and Prednisolone

Few studies have reported the changes in the peptide YY (PYY) levels in the intestinal tissue of rats with ulcerative colitis (UC) following oral administration of mesalazine and prednisolone. We investigated the effects of these drugs on the intestinal mucosal PYY levels in a rat model of UC. We confirmed that the PYY levels in the rat intestinal mucosal tissue were high in the lower intestinal tract. The leukocyte count and hemoglobin levels approached the normal values after administering mesalazine or prednisolone to rats treated with 3% dextran sulfate sodium (DSS). The PYY levels in the caecum and colon decreased significantly after administering DSS but increased when mesalazine was administered in a tissue-specific manner. Unlike mesalazine, the PYY levels increased in the ileum in addition to the colon and rectum after administering prednisolone. However, neither of the drugs induced any changes in the plasma PYY levels. These findings indicate that changes in the intestinal tissue PYY levels may be partially involved in the improvement of DSS-induced UC in rats following the administration of these drugs.

Changes of Intestinal Mucosal and Plasma PYY in a Diarrhea Model Rat and Influences of Loperamide as the Treatment Agent for Diarrhea

Peptide YY (PYY) is produced by endocrine cells in the lower gastrointestinal tract. The main functions of PYY are antisecretory effects in the colon and inhibition of gastrointestinal motility. We chose PYY as an index of the intrinsic factor in diarrhea and examined the influence of changes induced in a diarrhea rat model by administration of 4 types of laxative and loperamide hydrochloride (loperamide) as an agent for the treatment of diarrhea. A specific radioimmunoassay was performed to determine plasma and intestinal mucosal PYY concentrations. PYY in the rat intestinal tissue extract was distributed at a high density in the lower intestinal mucosa. In the diarrhea rat model, multiple changes in PYY concentrations in the intestinal mucosa and plasma were observed. In rats administered castor oil and sodium picosulfate, the intestinal mucosal PYY levels significantly decreased in a dose-dependent manner. Plasma PYY levels significantly decreased only in rats administered magnesium citrate. Next, we examined the influence of loperamide administration on the intestinal mucosa and plasma PYY concentrations in these rats. Loperamide administration resulted in multiple changes in plasma and intestinal mucosa PYY concentrations, along with an improvement in the diarrhea. Our research showed that the endocrine hormone PYY is involved in the onset of diarrhea, the course of the condition, and the manifestation of medicinal effects in the lower intestine.

Effect of Ileal Infusion of Short-Chain Fatty Acids on Pancreatic Prandial Secretion and Gastrointestinal Hormones in Pigs

Nutrients passing the ileum induce mechanisms regulating pancreatic secretion, but the effect of short-chain fatty acids (SCFAs) present in the ileum because of either intestinal fermentation or due to the cecoileal reflux is still unclear. This study investigated the effect of ileal SCFAs on pancreatic secretion and plasma levels of peptide YY, cholecystokinin, motilin, and neurotensin. The pigs were fitted with pancreatic duct, ileal, and jugular vein catheters, and a duodenal T-shaped cannula. Saline, 85.0 or 170.0 mM acetate, 5.0 or 10.0 mM butyrate, 7.5 or 15.0 mM propionate were infused into the ileum during feeding. The ileal infusions of SCFAs did not affect the pancreatic juice outflow and the lipase output. The protein output was lower when 10.0 mM butyrate or 170.0 mM acetate were infused. The trypsin output decreased for most of the SCFA infusions. The alpha-amylase output decreased for the infusion of 10.0 mM butyrate and tended to decrease for 170.0 mM acetate. The infusions did not change gut hormone level. Ileal SCFAs might induce an inhibition of pancreatic enzyme secretion under prandial conditions. Ileal SCFAs do not inhibit pancreatic secretion by a hormonal pathway involving the release of peptide YY, motilin, neurotensin, or cholecystokinin.

Peptide YY: A Gut Hormone Associated with Anorexia during Infectious Diarrhea in Children

To evaluate the effects of diarrhea on appetite among Peruvian children age 12 to 71 months and to assess whether elevated plasma levels of peptide YY, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta contribute to anorexia in this population. A total of 46 Peruvian children with diarrhea and 46 healthy controls underwent an observed feeding trial that was repeated when cases were healthy. Blood samples were obtained from 30 cases and 30 controls at the first trial and from 30 cases at the second trial and assayed for peptide YY, TNF-alpha, and IL-1beta. In the cases, mean consumption was less when sick than when healthy. The mean plasma level of peptide YY was higher for cases than controls and higher for cases when sick than when healthy. TNF-alpha levels were higher in cases than controls at visit 1 and also higher in cases when sick than when healthy. There were no differences in IL-1beta levels between cases and controls or between cases when sick and healthy. Peptide YY levels in children with diarrhea correlated with the likelihood of them eating less when sick than when healthy. Elevated serum peptide YY may be a mechanism for anorexia in children with diarrhea.

Peptide YY induces enterocyte proliferation in a rat model with total enteral nutrition after distal bowel resection

The main reason why enterocyte proliferative effects of peptide YY (PYY) have not been detected in rats undergoing massive small intestinal resection after feeding may have been the background activity of markedly increased endogenous PYY released from L cells in the distal gut in response to the intraluminal nutrients. The purpose of the present study was to evaluate the effects of PYY on enterocyte proliferation in a rat model of distal bowel resection (DBR) with total enteral nutrition (TEN). Male, adult Sprague-Dawley rats were assigned into three experimental groups: sham rats underwent bowel transection and reanastomosis, DBR rats underwent the resection of 40 cm distal small intestine and colon, and DBR-PYY rats underwent distal bowel resection as above, and were treated with PYY(1-36) from day 2 to day 14 postoperatively. During days 2-14 postoperatively, all animals received isocaloric TEN. At the endpoints, plasma PYY levels and parameters of enterocyte proliferation were determined. Compared with the sham group, DBR rats demonstrated a significant decrease in plasma PYY levels, and a significant increase in intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index. Administration of PYY (DBR-PYY group) led to a significant increase in plasma PYY levels, intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index in comparison with the DBR untreated group. We conclude that administration of PYY increases the plasma PYY levels, and PYY induces enterocyte proliferation with TEN after distal bowel resection.

Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure

Malnutrition is very prevalent among patients with chronic renal failure. The role of derangements in the gut-brain axis for regulation of appetite in the genesis of anorexia of these patients has not been adequately investigated. Design. Following a randomized, crossover design, we analysed plasma levels of peptide YY (PYY)(1-36) and PYY(3-36) both fasting and after a standardized oral mixed meal or intraperitoneal glucose infusion in 10 stable uraemic patients undergoing peritoneal dialysis and 8 healthy controls, matched for age, gender and body mass index. Main results. Median baseline plasma levels of PYY(1-36) in the different provocation tests oscillated between 406 and 460 pg/mL in patients, as compared with 73 and 100 pg/mL in controls (P < 0.001). Corresponding values for PYY(3-36) oscillated between 235 and 267 pg/mL in patients, versus 56 and 70 pg/mL in controls (P < 0.001). The association of high levels of PYY(3-36) and normal levels of acylated ghrelin (when compared with healthy controls) configurated a markedly pro-anorexigenic pattern in patients. Neither oral intake nor intraperitoneal glucose resulted in significant changes in plasma levels of PYY(1-36) or PYY(3-36) in subjects with renal failure, in contrast with the expected postprandial rise observed in healthy controls (41% for PYY(1-36), P = 0.04 and 32% for PYY(3-36), P = 0.02, median values). Baseline plasma levels of PYY(1-36) or PYY(3-36) are markedly elevated in patients with renal failure undergoing peritoneal dialysis. Provocation studies disclose a marked disregulation in the postprandial secretion of these anorexigenic peptides, when compared with healthy controls. These findings may contribute to clarify the complex pathogenesis of anorexia of chronic renal failure.

Peptide YY

Purpose of review Peptide YY, released from the gastrointestinal tract, has been shown to reduce food intake and bodyweight in rodents and to reduce food intake after intravenous infusion in humans. The purpose of this review is to highlight recent advances in the peptide YY field with regard to energy balance in both rodent and human models. Recent findings The anorexigenic effect of peripherally administered peptide YY3–36 in rodents has been confirmed by others. A number of groups have been unable to reproduce these original findings. Recent studies have suggested that the failure of an anorexigenic response to peptide YY3–36 may be explained, at least partly, by interference by incidental extraneous experimental stress. Peptide YY3–36 was initially hypothesized to alter food intake inhibiting neuropeptide Y appetite-stimulating pathways in the hypothalamus. If these pathways were already inhibited by incidental stress, peptide YY3–36 would have nothing further to inhibit. There is conflicting evidence as to whether peptide YY3–36 alters food intake via a direct circulation/hypothalamic interaction or via the vagal pathway. Recent studies have found that plasma peptide YY levels are elevated post-gastric bypass in obese individuals, which may be the cause of the resulting appetite loss post-surgery. Finally, peptide YY, when administered in combination with glucagon-like peptide-1, reduces food intake to a greater extent than either alone in rodent and human models, suggesting a possible combination therapy for reducing bodyweight. Summary Peptide YY reduces food intake in rodent and human models and plays a role in the homeostatic mechanisms underpinning energy balance.

Circulating Concentrations of Human Peptide YY: Influence of Acute and Chronic Energy Balance Changes

While the pharmacological potential of PYY3–36 to generate a negative energy balance is currently controversial, the regulation of PYY secretion in the regulation of energy balance is yet unclear. Intriguingly, a recent report indicating low peptide YY (PYY) plasma levels may justify PYY replacement therapy in diet induced human obesity. Plasma levels in lean (n=48, 25 male (m), 23 female (f) BMI: 22.7±0.5kg/m-2), anorectic (n=20, BMI: 15.2±0.2kg/m-2), obese (n=35, 16 m/19 f, BMI: 33.2±0.7kg/m-2) and morbidly obese (n=11, 1 m/10 f, BMI: 43.2±2.1kg/m-2) subjects as well as samples from obese patients before and after therapeutic weight loss (n=17, average DBMI: –4.2%; p<0.001) and anorectic patients before and after therapeutic weight gain (n=20, average DBMI: +14%) were analyzed. Changes in plasma PYY levels in six healthy individuals (3 m/3 f, age: 29±1.2, BMI: 20.7±1.1kg/m-2) were measured before and after ingestion of a high caloric meal. Total PYY levels were analyzed using a commercially available EIA assay (Diagnostic Systems Laboratories, DSL). Plasma PYY levels (all values mean±SEM) in patients with anorexia nervosa (92±8 pg/ml, p<0.05) were higher than those of lean (43±4 pg/ml), obese (41±6 pg/ml) or morbidly obese (47±16 pg/ml) individuals. Neither 4.2% weight loss in obese patients nor 14% weight gain in anorectic patients changed fasting plasma PYY levels. Postprandial PYY plasma levels in healthy volunteers increased within 15min to 250% of fasting levels and remained elevated for more than 90min after the meal as predicted, confirming the validity of the PYY assay used. We conclude that circulating PYY levels in humans may play a role in anorexia nervosa, a finding that merits further study. Our findings do not support a role for PYY in human obesity, and cast doubt on the effectiveness of PYY replacement therapy for obese patients. Nevertheless, it will be important to determine whether PYY3–36 is specifically reduced in obese people before abandoning this therapeutic approach.

Basal and fat-stimulated plasma peptide YY levels in celiac disease.

The distal gut hormone peptide YY (PYY) mediates feedback inhibition of gastric acid secretion, gastrointestinal motility, and pancreatic enzyme output. To investigate the influence of maldigestion on PYY, we determined plasma PYY levels in patients with celiac disease under basal conditions and in response to intraduodenal fat. Basal PYY was increased in untreated celiac patients (N = 13) compared to patients on a gluten free diet (N = 9) [15.6 (11.8-27.0) pM vs 12.2 (10.1-13.1) pM; P < 0.05] and compared to control subjects (N = 15) [9.5 (8.3-10.4) pM; P < 0.001]. Integrated PYY in response to intraduodenally infused predigested fat (1071+/-293 pM 80 min) was significantly (P < 0.05) greater than in response to undigested fat (322+/-223 pM 80 min) in six untreated celiacs. Plasma concentrations of PYY and cholecystokinin were strongly correlated (r = 0.79; P < 0.001). We conclude that basal PYY levels in untreated celiac disease are elevated, that predigestion of fat enhances PYY release in these patients, and that PYY secretion is correlated with CCK release.

Release of distal gut peptide YY (PYY) by fat in proximal gut depends on CCK☆

We tested the hypothesis that the release of PYY by fat confined to the proximal small intestine is dependent on CCK. Using a multi-fistulated model, plasma PYY levels were compared in 6 dogs after 60 mM oleate was perfused into the proximal one-half of the small intestine following i.v. administration of saline or devazepide, a CCK-A antagonist. Plasma PYY increased with fat ( P < 0.05), but plasma PYY level was lower following devazepide at 60 min and 90 min ( P < 0.05). We conclude that CCK serves as a foregut signal linking fat in the proximal gut with the release of distal gut PYY.

Morphological and immunohistochemical changes in intestinal mucosa and PYY release following total colectomy with ileal pouch-anal anastomosis in dogs.

Other studies have shown that both morphological and functional adaptation occur in the ileal mucosa after total colectomy and may be mediated by humoral factors. To elucidate the participation of peptide YY (PYY) in intestinal adaptation after total proctocolectomy with ileal pouch-anal anastomosis (IPAA), changes in the number of PYY-containing cells and in histological appearance in the intestinal mucosa, especially in the mucosa of ileal pouch, were investigated in dogs. We further examined changes in postprandial PYY release in relation to those in PYY-containing cells. Ten adult beagle dogs underwent IPAA. Before and 2, 6, and 12 months after surgery, a test meal was given, and blood samples were taken from a foreleg vein at intervals for 3 hr for measurements of plasma PYY concentration by radioimmunoassay. Before and one year after surgery, morphological studies of the intestinal mucosa were performed using parameters such as villous height (VH), mucosal thickness (MT), and villous index (VI). Immunohistochemical studies of PYY were also done in the intestinal mucosa. Both fasting and postprandial plasma PYY levels were reduced to half of the preoperative levels at two months after surgery. Thereafter, postprandial levels approached preoperative concentrations, while fasting levels remained unchanged. VH, MT, and VI were significantly smaller in the ileal pouch than in the ileal end of the controls. The MT of the ileal pouch was similar to that of the colon. PYY-containing cells in the mucosa of the ileal pouch were distributed more densely than those in the ileal end, similar to those in the colon of the controls. It was concluded that after IPAA, the pouch mucosa gradually changed to resemble the colonic mucosa not only in histological appearance but also in the population of PYY-containing cells. It is therefore considered that colonic transformation of the ileal-pouch mucosa is closely related to the increase in the number of PYY-containing cells and the steady recovery of postprandial PYY secretion.

Duodenal motility in fasting dogs: humoral and neural pathways mediating the colonic brake.

We have previously described a negative feedback loop that inhibits duodenal motility when nutrients are infused into the ileum and colon. In the present study, we examined the role of extrinsic innervation and plasma levels of peptide YY (PYY) in mediating this phenomenon. We perfused neurally intact (n = 5 dogs) or extrinsically denervated (n = 6 dogs) isolated loops of proximal colon with isomolar NaCl or a mixed-nutrient solution at 2 and 6 ml/min for 4 h during fasting or for 2 h beginning 15 min after a meal. Both rates of infusion with NaCl prolonged the cycle length of the duodenal migrating motor complex (MMC) in the group with neurally intact loops but not in the group with extrinsically denervated loops. Nutrient infusions increased the MMC cycle length in both groups. Integrated plasma concentrations of PYY were increased by nutrients but not by NaCl in both groups. These data suggest that increased volumes and unabsorbed nutrients in the proximal colon alter proximal small bowel motility. Volume-induced effects are mediated via extrinsic nerves, whereas nutrient-induced effects may be mediated by humoral factors, such as plasma PYY.