Plasma Peptide YY Concentrations Research Articles

Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study

Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY.Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes.Methods: 136 adults with pre-diabetes and a body mass index of ≥25 kg/m2 underwent a 2-month weight-reducing total meal replacement diet. Participants who lost ≥8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months.Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of ~50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain.Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet.Clinical Trial Registry: ClinicalTrials.gov registry ID NCT01777893 (PREVIEW) and ID NCT02030249 (Sub-study).

Enolase inhibition alters metabolic hormones and inflammatory factors to promote neuroprotection in spinal cord injury

Enolase inhibition is a potential therapeutic strategy currently being investigated for treatment of spinal cord injury (SCI) as it reduces pro-inflammatory cytokines and chemokines, alters metabolic factors, and reduces gliosis in acute SCI. Herein, the role of enolase in SCI has been examined to better understand the effects of this enzyme on inflammation, metabolic hormones, glial cell activation, and neuroprotection under these shorter injury conditions. Immunohistochemical analyses of inflammatory markers vimentin, Cox-2, and caspase-1 indicated that enolase inhibition attenuated the elevated levels of inflammation seen following SCI. Iba1, GFAP, NFP, and CSPG staining indicated that enolase inhibition with prolonged administration of ENOblock reduced microglia/astrocyte activation and lead to enhanced neuroprotection in SCI. An analysis of metabolic hormones revealed that ENOblock treatment significantly upregulated plasma concentrations of peptide YY, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, glucagon, and insulin hormones as compared to vehicle-treated controls (Mann-Whitney, p ≤ 0.05). ENOblock did not have a significant effect on plasma concentrations of pancreatic polypeptide. Interestingly, ENOblock treatment inhibited chondroitin sulfate proteoglycan (CSPG), which is produced by activated glia and serves to block regrowth of axons across the lesion site following injury. An increased level of NeuN and MBP with reduced caspase-1 was detected in SCI tissues after ENOblock treatment, suggesting preservation of myelin and induction of neuroprotection. ENOblock also induced improved motor function in SCI rats, indicating a role for enolase in modulating inflammatory and metabolic factors in SCI with important implications for clinical consideration.

Oat beta-glucan as a dietary supplement for dogs.

The aim of this study was to evaluate the effects of oat beta-glucan supplementation on metabolic, physiological, immunological and nutritional variables in adult dogs. Fourteen dogs were fed a control diet or a diet supplemented with 1% beta-glucan during 71 days. Serum concentrations of glucose, total cholesterol and lipoprotein fractions, as well as plasma concentrations of peptide YY and ghrelin, were determined. In addition, coefficient of total tract apparent macronutrient digestibility (CTTAD), food intake and fecal output, score, and pH were evaluated. For evaluation of immunological variables, serum concentrations of interleukin-4 and interferon gamma were determined on days 0, 57 and 71, which corresponded to blood collection prior to beta-glucan supplementation, and at 7 and 14 days post first and second dose of vaccination (Pneumodog®, Merial, Campinas, Brazil), respectively. Animals fed the supplemented diet showed (P<0.05) lower serum concentrations of total cholesterol and low and very low density lipoproteins, lower coefficients of total tract apparent digestibility of dry matter, organic matter, mineral matter and ether extract, higher fecal output and lower fecal consistency, as well as a tendency (P = 0.07) of decreasing the coefficient of total tract apparent digestibility of crude protein. Moreover, the supplemented diet resulted in lower number of red blood cells, hematocrit percentage and hemoglobin concentration 21 days post-vaccination as well as lower serum concentration of interleukin-4 seven days post-vaccination (P<0.05). It is concluded that oat beta-glucan extract can be used as a dietary supplement for dogs at a dose of 10 g/kg of food, being effective in reducing blood concentrations of total cholesterol, LDL-c and VLDL-c as well as CTTAD of nutrients, demonstrating a potential to be used in the feeding of obese animals. In addition, by reducing the predominance of a Th2 response, oat beta-glucan can positively modulate the vaccine response of animals.

Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats.

Dairy proteins-whey protein, in particular-are satiating and often recommended for weight control; however, little is known about the mechanisms by which whey protein and its components promote satiety and weight loss. We used diet-induced obese rats to determine whether the hypophagic effects of diets that are enriched with whey and its fractions, lactalbumin and lactoferrin, are mediated by the gut hormone, peptide YY (PYY). We demonstrate that high protein diets that contain whey, lactalbumin, and lactoferrin decreased food intake and body weight with a concurrent increase in PYY mRNA abundance in the colon and/or plasma PYY concentrations. Of importance, blockade of PYY neuropeptide Y receptor subtype 2 (Y2) receptors with a peripherally restricted antagonist attenuated the hypophagic effects of diets that are enriched with whey protein fractions. Diets that are enriched with whey fractions were less preferred; however, in a modified conditioned taste preference test, PYY Y2 receptor blockade induced hyperphagia of a lactoferrin diet, but caused a reduction in preference for Y2 antagonist-paired flavor, which suggested that PYY signaling is important for lactoferrin-induced satiety, but not essential for preference for lactoferrin-enriched diets. Taken together, these data provide evidence that the satiety of diets that are enriched with whey protein components is mediated, in part, via enhanced PYY secretion and action in obese male rats.-Zapata, R. C., Singh, A., Chelikani, P. K. Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats.

Glucagon-like peptide-1 (GLP-1) increases in plasma and colon tissue prior to estrus and circulating levels change with increasing age in reproductively competent Wistar rats

There is a well-documented association between cyclic changes to food intake and the changing ovarian hormone levels of the reproductive cycle in female mammals. Limited research on appetite-controlling gastrointestinal peptides has taken place in females, simply because regular reproductive changes in steroid hormones present additional experimental factors to account for. This study focussed directly on the roles that gastrointestinal-secreted peptides may have in these reported, naturally occurring, changes to food intake during the rodent estrous cycle and aimed to determine whether peripheral changes occurred in the anorexigenic (appetite-reducing) hormones peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1) in female Wistar rats (32–44 weeks of age). Total forms of each peptide were measured in matched fed and fasted plasma and descending colon tissue samples for each animal during the dark (feeding) phase. PYY concentrations did not significantly change between defined cycle stages, in either plasma or tissue samples. GLP-1 concentrations in fed plasma and descending colon tissue were significantly increased during proestrus, just prior to a significant reduction in fasted stomach contents at estrus, suggesting increased satiety and reduced food intake at this stage of the cycle. Increased proestrus GLP-1 concentrations could contribute to the reported reduction in food intake during estrus and may also have biological importance in providing the optimal nutritional and metabolic environment for gametes at the potential point of conception. Additional analysis of the findings demonstrated significant interactions of ovarian cycle stage and fed/fasted status with age on GLP-1, but not PYY plasma concentrations. Slightly older females had reduced fed plasma GLP-1 suggesting that a relaxation of regulatory control of this incretin hormone may also take place with increasing age in reproductively competent females.

Small intestinal protein infusion in humans: evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release.

Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of gastrointestinal peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins. To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion. Fourteen subjects (four male, mean age: 23±2.1 years, mean body mass index: 21.6±1.8 kg m-2) were intubated with a naso-ileal catheter in this double-blind, randomized, placebo-controlled crossover study. Test days (four in total, executed on consecutive days) started with the ingestion of a standardized breakfast, followed by the infusion of 15 g of protein in the duodenum, jejunum or ileum over a period of 60 min. Food intake was measured by offering an ad libitum meal and Visual Analogue Scale (VAS) scores were used to assess feelings of hunger and satiety. Blood samples were drawn at regular intervals for CCK, GLP-1, PYY, glucose and insulin analyses. Intraileal protein infusion decreased ad libitum food intake compared with both intraduodenal and placebo infusion (ileum: 628.5±63 kcal vs duodenum: 733.6±50 kcal, P<0.01 and placebo: 712.2±53 kcal, P<0.05). GLP-1 concentrations were increased after ileal infusion compared with jejunal and placebo infusion, whereas CCK concentrations were only increased after intraileal protein infusion compared with placebo. None of the treatments affected VAS scores for hunger and satiety nor plasma concentrations of PYY and glucose. Protein infusion into the ileum decreases food intake during the next meal compared with intraduodenal infusion, whereas it increases systemic levels of GLP-1 compared with protein infusion into the jejunum and placebo respectively.

Plasma Concentrations of GLP-1 and PYY in Rats Fed Dietary Fiber Depend on the Fermentability of Dietary Fiber and Respond to an Altered Diet

Background: It was reported to be associated with intake of dietary fiber and gut hormone. We compared the effect of dietary fiber on the plasma concentration of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Methods: Firstly, male Wistar rats (10 wk old) were fed a fiber-free diet (FF diet, AIN-93G-based diet without cellulose) or one of nine FF diets with 5% dietary fiber for 21 days. Cellulose, guar gam (GG), partially hydrolyzed guar gum (PHGG), sugar beet fiber (BF), konjac mannnan (KM), raffinose (RF), hydroxypropyl starch (HPS), hydroxypropyl distarch phosphate (HPDP) and Akamoku (AK) were used as dietary fiber sources. Secondly, we then determined whether the concentrations of GLP-1 and PYY in portal and aorta plasma and microbiota in cecal contents responded to an altered diet. Male Wistar rats (10 wk old) were fed the PHGG diet for 20 days before being changed to the FF diet. Results: The amount of short chain fatty acids (SCFA) in the cecal contents markedly increased in rats fed the GG, PHGG, BF, KM, RF, HPS or HPDP diets compared with SCFA in rats fed the FF, CL or AK diets. The concentrations of GLP-1 and PYY in portal plasma positively correlated with the concentration of SCFA in the cecal contents and cecal tissue weight. The concentrations of GLP-1 and PYY, in the altered diet group decreased to the same concentration as that measured in the FF group. However, it was low the similarities in the cecal bacteria population. Conclusion: The plasma concentrations of GLP-1 and PYY increased with increasing the amounts of SCFA, the products of DF fermentation, in the cecal contents. GLP-1 and PYY plasma concentrations and SCFA concentrations in the cecal contents rapidly responded to the altered diet, but the cecal bacteria population did not.

Circulating concentrations of glucagon-like peptide 1, glucose-dependent insulinotropic peptide, peptide YY, and insulin in client-owned lean, overweight, and diabetic cats

Our objectives were to measure plasma concentrations of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) in client-owned newly diagnosed diabetic cats and nondiabetic lean or overweight cats and to determine whether circulating concentrations of these hormones differed between study groups and if they increased postprandially as seen in other species. A total of 31 cats were recruited and placed into 1 of 3 study groups: lean (body condition score 4–5 on a scale of 1–9; n = 10), overweight (body condition score 6–8; n = 11), or diabetic (n = 10). Diabetics were newly diagnosed and had not had prior insulin therapy. Preprandial (fasting) and postprandial (60 min after meal) plasma hormone and glucose concentrations were measured at baseline and 2 and 4 wk. All cats were exclusively fed a commercially available high-protein and low-carbohydrate diet commonly prescribed to feline diabetic patients for 2 wk before the 2-wk assessment and continued through the 4-wk assessment. Results showed that plasma concentrations of GLP-1, GIP, PYY, and insulin increased in general after a meal in all study groups. Plasma PYY concentrations did not differ (P > 0.10) between study groups. Diabetics had greater plasma concentrations of GLP-1 and GIP compared with the other study groups at baseline (P < 0.05), and greater preprandial and postprandial GLP-1 concentrations than lean cats at 2 and 4 wk (P < 0.05). Preprandial plasma GIP concentrations were greater in diabetics than obese and lean (P < 0.05) cats at week 4. Postprandial plasma GIP concentrations in diabetics were greater than lean (P < 0.05) at week 2 and obese and lean cats (P < 0.05) at week 4. Together, our findings suggest that diabetic status is an important determinant of circulating concentrations of GLP-1 and GIP, but not PYY, in cats. The role of GLP-1, GIP, and PYY in the pathophysiology of feline obesity and diabetes remains to be determined.

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.

Comparison of the Effects of Roux-en-Y Gastric Bypass and Ileal Transposition Surgeries on Food Intake, Body Weight, and Circulating Peptide YY Concentrations in Rats

Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatments for obesity producing long-term weight loss. The anorexia and weight loss from RYGB could be due to gastric restriction, malabsorption, enhanced lower gut stimulation, increased energy expenditure, and/or other metabolic adaptations. In ileal transposition (IT) surgery, a segment of the ileum is transposed to the upper jejunum with no gastric restriction or malabsorption. Our objective is to compare the effects of RYGB and IT surgeries on food intake, body weight, and plasma concentrations of the anorexigenic lower gut hormone Peptide YY (PYY) in rats. Adult male Sprague-Dawley rats were subjected to either RYGB (n = 9), IT (n = 9) or sham surgeries (n = 16). A subset of sham animals were either pair-fed to RYGB (n = 9) or ad lib fed (n = 7) on a highly palatable mixed nutrient liquid food (Ensure). Food intake, body weight and plasma PYY concentrations were measured. The data demonstrate that (1) RYGB produces a sustained reduction in food intake and weight gain, (2) the anorexic effects of IT are relatively transient lasting for 5 weeks, (3) the reduction in weight gain resulting from IT is similar to that of animals pair-fed to RYGB, and (4) RYGB and IT surgeries are associated with elevated postprandial plasma PYY concentrations. We demonstrate in our rat models that RYGB surgery produces a greater reduction in food intake and weight gain than IT surgery, and that both surgeries are associated with enhanced plasma concentrations of Peptide YY.

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.

Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: Postprandial effect on circulating gut peptides, glucose and insulin

Gut hormones [ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1)] are an important group of hormones that target appetite control. They are released from endocrine L cells of the small bowel in proportion to the volume, components and calories in a meal. In the current study, 20 g of gelatin (flavored and sweetened) were given to obese patients (n=12) and lean subjects (n=10). Subsequently, plasma samples were collected at-30- minute intervals up to 180 minutes and glucose, insulin, PYY, GLP-1 and ghrelin were assayed using specific and sensitive immunofluorometric and radioimmunoassays. As expected, obese patients had normal serum glucose levels, higher serum insulin, and lower plasma concentration of ghrelin at all times compared to lean subjects. GLP-1 plasma levels were significantly elevated at 60 minutes, peaking at 120 minutes in obese patients and lean subjects. As a consequence, there was a significant rise in serum insulin levels with a significantly higher peak level at 60 min (obese) and 30 min (lean). There were no significant changes in PYY plasma concentrations and no correlation was found between body mass index and concentrations of ghrelin, PYY and GLP-1 in the group of obese patients. In conclusion, a single gelatin meal induces a rise in plasma GLP-1 followed by an increase in serum levels of insulin. These findings may be applied to maximize satiety in obese patients as a means of improving adherence to calorie-controlled diets as well as provide better control of diabetic patients.

Peptide‐YY Levels after a Fat Load in Black and White Women

To determine whether basal plasma peptide-YY (PYY) levels in overweight, middle-aged black women are different from those of white women of similar BMI and age and ascertain whether there is a difference between the two groups in plasma PYY levels in response to a liquid high fat load. Using a commercial radioimmunoassay kit, the concentration of PYY was measured at baseline and at 2, 4, 6, and 8 hours after ingesting a fatty liquid meal (86.5% of the calories from fat) in 12 black and 12 white women who were matched for age and BMI. PYY levels (picograms per milliliter) at baseline and at every other time-point of the test meal were significantly lower in the black than in the white group. In addition, the change in PYY concentration from baseline was lower in the black than in the white group only at 8 hours after the meal. The lower baseline level and the blunted PYY response of the black women to the fat load indicated that this signal for appetite suppression was reduced, which, in turn, might contribute to the enhanced obesity of the black women.

Mediators for fat-induced ileal brake are different between stomach and proximal small intestine in conscious dogs

Our aim was to determine the mechanisms by which intraileal fat alters proximal gastrointestinal motility—the ileal brake. Five mongrel dogs with ileal Thiry-Vella fistulas were equipped with strain gauge force transducers on the upper gut to measure contractile activity. Ileal infusions of 115 mmol/L oleic acid and triglyceride were studied in dogs with extrinsically innervated and extrinsically denervated Thiry-Vella loops. Plasma concentrations of peptide YY and total glucagon-like immunoactivity were measured. Oleic acid but not triglyceride inhibited postprandial contractions in the gastric antrum in dogs with innervated and denervated Thiry-Vella loops. Postprandial duodenal and jejunal motility was inhibited by oleic acid regardless of extrinsic denervation to the loops ( P <0.05), but triglyceride inhibited small intestinal motility only in dogs with innervated Thiry-Vella loops. Intraileal oleic acid but not triglyceride increased plasma concentrations of peptide YY and total glucagon-like immunoactivity in dogs with innervated and denervated Thiry-Vella loops. Intraileal oleic acid inhibits gastric and small intestinal motility possibly via increased plasma concentrations of peptide YY and enteroglucagon. Intact extrinsic innervation is necessary for intraileal triglyceride to inhibit small intestinal motility.

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.

Impaired Release of Peptide YY in Patients with Proctocolectomy and Ileal Pouch-Anal Anastomosis

Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels. Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects. Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 +/- 0.3 versus 9.3 +/- 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 +/- 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 +/- 66 pM*180min versus 3194 +/- 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001). PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous 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.

Selective Nutrient Feeding Induces Maturation of Gastrointestinal Hormone Release in Preterm Infants • 1498

We have previously shown that preterm infants given small enteral feedings have higher plasma concentrations of gastrin and gastric inhibitory peptide(GIP), while plasma concentrations of peptide YY (PYY) are unchanged. In adults, the ingestion of protein stimulates the release of gastrin which, in turn, stimulates the release of acid and stimulates an increase in gastroduodenal motor activity. Carbohydrate stimulates the release of GIP which regulates plasma glucose and inhibits small intestinal motor activity. Fats stimulate the release of PYY which inhibits small intestinal motor activity. We speculated that feeding babies with selective nutrients would induce hormone release in preterm infants as they do in adults, and, thus, enhance gastrointestinal function. Eighty preterm infants 25 to 30 wks gestation admitted to the Newborn Intensive Care Unit at Ben Taub General Hospital were fed 24 ml/kg/d for the first 10 days they received enteral feedings in addition to parenteral nutrition. Infants were given one of 4 formulas: full 24 cal/oz formula (n=20), its carbohydrate (n=20), protein(n=20), or fat component (n=20), all fed in 4 hr cycles consisting of 2 hr infusions interrupted by 2 hrs of fasting. On the tenth study day, blood was drawn to determine fasting plasma concentrations of gastrin, GIP, and PYY. In addition, motor responses to a full strength formula feeding were assessed via a low compliance continuous perfusion manometry. Compared to values seen at birth, fasting plasma concentrations of gastrin increased by feeding day 10 among infants fed protein, fat, or full formula (all p<0.05, paired t test) but not carbohydrate. GIP plasma concentrations increased in babies fed carbohydrate or full formula (both p<0.05) but not fat or protein. Plasma concentrations of peptide YY did not change in any feeding group. No group of study infants displayed the presence of a motor response to feeding before enteral feedings were begun. Babies fed protein or full formula displayed motor responses to feeding after 10 days of feeding while babies fed carbohydrate and fat did not. We conclude that the release of gastrointestinal hormones in response to selective nutrients is present in preterm infants, as well as motor responses to feeding that are mediated by those nutrients. We speculate that designing formulas that trigger intestinal hormonal release may be useful in enhancing the infant's endogenous mechanisms to improve gastrointestinal function.

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.

Role of extrinsic innervation in carbohydrate-induced ileal modulation of pancreatic secretion and upper gut function.

Previously we showed that carbohydrate (CHO) in the ileum slowed gastric emptying and increased pancreatic amylase secretion relative to that of other enzymes. Our aim here was to determine if extrinsic innervation of the jejunoileum participates in the CHO-induced ileal modulation of postprandial upper gut function. Six dogs were studied before and 2-3 weeks after in situ neural isolation of the jejunoileum (complete extrinsic denervation). Gastric emptying (GE) and pancreatic amylase secretion were quantitated for 4 h after a 300-ml meal containing 3H-PEH (liquid marker) and 99mTc sulfur colloid cooked with eggs (solid marker). Coincident with feeding, we started a distal ileal infusion of 150 mM NaCl or 40 mg.min-1 CHO. Extrinsic denervation abolished the slowing of GE of liquids and solids and the augmented increase in amylase and trypsin in relation to solid emptying seen in the neurally intact dogs prior to denervation. Denervation also abolished the decrease in total pancreatic exocrine secretion in response to ileal CHO. Increases in plasma concentrations of peptide YY (PYY) were correlated temporally with decreased GE of solids and increased exocrine secretion during ileal CHO in neurally intact dogs, but no increases in PYY release occurred after extrinsic denervation. Extrinsic denervation of the jejunoileum abolished the effect of ileal CHO on GE of liquids and solids, the decrease in total amylase secretion during ileal CHO, and the relative increase in enzyme secretion expressed as total enzyme output per percentage solid marker emptied. Extrinsic innervation of the jejunoileum mediates ileal modulation of GE and the relationship of amylase secretion to GE of solids. The mechanism of this effect may be via neurally mediated release of PYY.