The cckOMA syndrome and its relation to the Zollinger-Ellison syndrome: a diagnostic challenge.

OBJECTIVE: Among patients with enteropancreatic neuroendocrine tumor syndromes only one case with a cholecystokinin (CCK) secreting tumor has been reported. She had significant hyperCCKemia leading to a specific syndrome of severe diarrheas, weight loss, repeated duodenal ulcers and a permanently contracted gallbladder with gallstones. There are, however, reasons to believe that further CCKomas exist, for instance among Zollinger-Ellison patients with normal plasma gastrin concentrations. The present review is a call to gastroenterologists for awareness of such CCKoma patients. METHOD: After a short case report, the normal endocrine and oncological biology of CCK is described. Subsequently, the CCKoma symptoms are discussed with particular reference to the partly overlapping symptoms of the Zollinger-Ellison syndrome. In this context, the diagnostic use of truly specific CCK and gastrin assays are emphasized. The discussion also entails the problem of access to accurate CCK measurements. CONCLUSION: Obviously, the clinical awareness about the CCKoma syndrome is limited. Moreover, it is also likely that the knowledge about the necessary specificity demands of diagnostic gastrin and CCK assays have obscured proper diagnosis of the CCKoma syndromes in man.

Increased Meal Size but Reduced Meal-Stimulated Plasma Cholecystokinin Concentrations in Women With Obesity.

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [-87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity.

Resting and postpradial serum cholecystokinin concentrations and evaluation of the effect of seeing and/or smelling food on serum cholecystokinin and bile acid concentrations in healthy dogs.

Serum bile acids concentrations rise postprandially. However, some dogs show paradoxical serum bile acids results with higher pre-prandial than post-prandial concentrations. The aim of this study was to evaluate serum cholecystokinin (CCK) concentrations and determine whether they correspond to paradoxical serum bile acids concentrations. In addition, seeing and smelling food was investigated as a possible cause for paradoxical serum bile acids results. Eight healthy dogs owned by volunteers enrolled in this experimental study. Food was withheld from the dogs for 12 h with great care not to expose them to any sight or smell of food. Blood samples were collected at 0, 30, 60, 120, 180, 240, 480 and 720 min after feeding. Food was then withheld again for 24 h, and blood samples were collected at 0, 30, 60, 120, 180, 240, 480 and 720 min after seeing and smelling food. After feeding, serum CCK concentrations increased, but paradoxical serum CCK concentrations were observed in some of dogs, but only one of those had also paradoxical serum bile acids concentrations. After seeing and smelling food, serum CCK and serum bile acids concentrations did not significantly increase. In conclusion, paradoxical serum CCK concentrations can occur in some healthy dogs after feeding. However, no correlation with paradoxical serum bile acids concentrations was found. Seeing or smelling food are unlikely causes for paradoxical serum bile acids concentrations. Additional studies are warranted to further evaluate the relationship of serum CCK and bile acids concentrations in healthy dogs and dogs with gastrointestinal disease.

Entero-Pancreatic Hormone Secretion, Gastric Emptying, and Glucose Absorption After Frequently Sampled Meal Tests.

CONTEXT: Entero-pancreatic hormone secretion has been reported during the pre-absorptive cephalic and gastric meal phases, but never with a blood sampling frequency providing a temporal resolution that allows close scrutiny and correlations with gastric emptying and glucose absorption. OBJECTIVE: We hypothesized that entero-pancreatic hormone secretion after nutrient ingestion would be rapid and correlate with gastric emptying and glucose absorption. METHODS: During 2 visits in a clinical research facility, 10 healthy young men ingested a 75-g glucose drink (OG) and a liquid mixed meal (LMM) (t = 0-2 minutes) on separate days. Acetaminophen and 3-O-methyl-D-glucopyranose (3-OMG) were added to the drinks to evaluate gastric emptying and glucose absorption, respectively. Arterialized venous blood was sampled (t = -30, -20, -18, -16, -14, -12, -10, -8, -6, -4, -2, 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 30 minutes). Plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), gastrin, cholecystokinin (CCK), glucagon, pancreatic polypeptide (PP), 3-OMG, and glucose were measured, as were serum insulin, C-peptide, and acetaminophen. RESULTS: Acetaminophen increased 8 minutes after OG (P < 0.001) and LMM (P < 0.05); 3-OMG, 8 minutes after LMM (P < 0.0001), 10 minutes after OG (P = 0.04); PP, 4 minutes after LMM (P < 0.03); gastrin, 6 minutes after LMM (P < 0.003) and OG (P < 0.003); CCK, 6 minutes after LMM (P = 0.0001); GIP, 8 minutes after OG (P < 0.05) and LMM (P < 0.03); glucose, 8 minutes after OG (P < 0.001); 12 minutes after LMM (P < 0.02); GLP-1, 12 minutes after OG (P < 0.01), 10 minutes after LMM (P < 0.01); insulin, 12 minutes after LMM (P = 0.02) and OG (P = 0.002); C-peptide, 12 minutes after OG (P = 0.002) and LMM (P = 0.04). CONCLUSION: Early postprandial hormone responses show characteristic differences with regard to timing and amplitude but also great individual differences. This should be considered when interpreting mean responses and designing study protocols.

The gastrointestinal tract in hunger and satiety signalling.

BACKGROUND: Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. METHODS: Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling. RESULTS: Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake. CONCLUSION: Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.

Hypoxia transactivates cholecystokinin gene expression in 3D-engineered muscle.

At high altitudes, the hypoxic atmosphere decreases the oxygen partial pressure in the body, inducing several metabolic changes in tissues and cells. Furthermore, it exerts potent anorectic effects, thus causing an energy deficit. Two decades ago, a marked increase in the resting level of plasma cholecystokinin (CCK) was observed in humans at the Mt. Kanchenjunga basecamp, located at 5100 m above the sea level, compared to sea-level control values. Interestingly, acute exercise also raises plasma CCK and exerts potent anorectic effects under normoxic conditions. However, the transcriptional regulations of Cck gene underlying these effects have not yet been established. Here, we employed acute electrical pulse stimulation (EPS) followed by microarray analysis to discover novel myokines in 3D-engineered muscle. Acute EPS affects the contractile function, inducing a decline in the contractile force. Surprisingly, microarray analysis revealed an EPS-induced activation of cholecystokinin receptor (CCKR)-mediated signaling. Furthermore, Cck was constitutively upregulated in 3D-engineered muscle, and its expression increased under hypoxic conditions. Notably, a hypoxia-responsive element was detected in the Cck promoters of mice and humans. Our results suggested that hypoxia transactivated Cck expression in 3D-engineered muscle. Furthermore, the elevation in plasma CCK levels following acute exercise or at high altitude might be partly attributed to myogenic cells.

Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study.

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.

Pancreatobiliary Diversion in the Mouse.

The gut hormone cholecystokinin (CCK) is primarily secreted from I-cells in the duodenum and proximal jejunum. CCK secretion is stimulated by food digests and inhibited by proteases from pancreatic juice. CCK regulates digestion and appetite, stimulates pancreatic growth, and participates in pancreatic carcinogenesis. The molecular mechanisms of CCK-induced effects are not fully understood. When the mechanisms are studied in animals, the surgical model of pancreatobiliary diversion (PBD) is frequently used. After animals have had PBD, their CCK secretion is no longer inhibited by pancreas-derived proteases, so circulating CCK is increased. PBD is established in rats and hamsters, but not in mice. In this study, we modified PBD procedures and established the model in the mouse. In an experiment, we performed PBD and sham operation (SO) in two groups of mice (20 mice per group). Twenty days after operation, 75% of the PBD mice and all SO mice survived. When plasma CCK was determined by radioimmunoassay, the PBD group had higher levels than the SO group (p < 0.001). To assess pancreatic growth, we determined pancreatic weight and pancreatic contents of protein and DNA. We also stained pancreatic sections by immunohistochemistry to show the proliferating cells that either expressed the proliferating cell nuclear antigen or were labeled with 5-bromo-2'-deoxyuridine. As a result, the pancreases of the PBD mice were heavier (p < 0.001) and had more protein (p < 0.001), DNA (p < 0.01), and proliferating cells (p < 0.01) than those of the SO counterparts. Thus, pancreatic growth was increased as a result of PBD-induced hypercholecystokininemia. The plasma and pancreatic data demonstrated that the PBD model was a success. This model may be used in CCK-related research. For instance, pancreatic cancer is frequently studied in transgenic mice. PBD may be combined with the cancer model to study the role of CCK in the molecular biology of pancreatic cancer.

Sweet Taste Antagonist Lactisole Administered in Combination with Sucrose, But Not Glucose, Increases Energy Intake and Decreases Peripheral Serotonin in Male Subjects.

Knowledge regarding the involvement of sweetness perception on energy intake is scarce. Here, the impact of glucose and sucrose sweetness, beyond their caloric load, on subsequent food intake and biomarkers of satiation was evaluated by co-administration of the sweet taste receptor inhibitor lactisole. A total of 27 healthy, male subjects received solutions of either 10% glucose w/o 60 ppm lactisole or 10% sucrose w/o 60 ppm lactisole. Subsequent food intake from a standardized breakfast was evaluated 2 h after receiving the respective test solution. Changes in postprandial plasma concentrations of cholecystokinin, ghrelin, and serotonin were determined over a period of 120 min, as was the body temperature. Administration of lactisole to the sucrose solution increased the energy intake from the subsequent standardized breakfast by 12.9 ± 5.8% (p = 0.04), led to a decreased Δ AUC of the body core temperature by 46 ± 20% (p = 0.01), and time-dependently reduced Δ serotonin plasma concentrations (-16.9 ± 6.06 ng/mL vs. -0.56 ± 3.7 ng/mL after sucrose administration, p = 0.03). The present study shows that lactisole increases energy intake and decreases plasma serotonin concentrations as well as body core temperature induced by sucrose, but not glucose. This finding may be associated with the different binding affinities of sucrose and glucose to the sweet taste receptor.

Circadian variations in plasma concentrations of cholecystokinin and gastrin in man.

Cholecystokinin (CCK) is a gut hormone which regulates gallbladder contraction and pancreatic enzyme secretion. In addition, CCK is also a major intestinal satiety signal. The knowledge about CCK in circulation, however, has been limited by difficulties in accurate measurement of the concentrations in plasma. Thus, CCK circulates in low concentrations and furthermore, it is structurally homologous to the antral hormone, gastrin, which circulates in higher concentrations. Therefore, most antibodies raised against CCK cross-react in immunoassays with gastrin. However, using highly sensitive and entirely specific in-house radioimmunoassays, which meet these challenges, we have now measured the daily concentration-variations of CCK and gastrin in plasma from young healthy men (n = 24). Plasma was sampled every third hour from each person during 24 h. The results show that the gastrointestinal secretion of both CCK and gastrin in man display significant circadian variations.

Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma.

Human studies have demonstrated that physiologically relevant changes in circulating glucagon-like peptide-1 (GLP-1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut-kidney axis, responsible for a rapid-acting feed-forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP-1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12-hr fasting period. Arterial blood samples were collected at 10-20-min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty-four-hour baseline urinary sodium excretions were similar between study days. Arterial GLP-1 levels increased during both oral glucose loads and were significantly higher at the 40-80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose-dependent insulinotropic polypeptide as well as glucose, insulin, and C-peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP-1 was higher (60-80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP-1 plasma concentration. Thus, GLP-1 may be part of an acute feed-forward mechanism for natriuresis.

Effects of intragastric tryptophan on acute changes in the plasma tryptophan/large neutral amino acids ratio and relationship with subsequent energy intake in lean and obese men.

Circulating tryptophan/large neutral amino acids (tryptophan/LNAA) ratio, an indicator of brain serotonin levels, may be important in appetite regulation, together with gastrointestinal (gastric emptying, plasma cholecystokinin) mechanisms. We have compared effects of intragastric tryptophan ('Trp') on the plasma tryptophan/LNAA ratio in lean and obese men, and the associations of the tryptophan/LNAA ratio, gastric emptying and CCK concentrations with energy intake. Lean and obese male participants (n = 16 each) received 3 g Trp or volume-matched control intragastrically, 15 min before a mixed-nutrient drink (300 mL, 400 kcal) (t = 0 min) in randomised, double-blind fashion. Plasma amino acid (for calculation of the plasma tryptophan/LNAA ratio) and CCK concentrations were measured from t = -20-60 min. Gastric emptying was assessed from t = 0-60 min, and ad-libitum energy intake from a standardised buffet-style meal from t = 60-90 min. The increase in the plasma tryptophan/LNAA ratio was less in obese, than lean, participants (P < 0.05), and greater in lean participants who reduced their energy intake (by >0 kcal) after Trp compared with those who did not (by ≤0 kcal) (P < 0.05). Moreover, in participants who reduced their energy intake, the ratio was lower in obese, than in lean (P < 0.05). There was a trend for an inverse correlation between energy intake with the plasma tryptophan/LNAA ratio in lean (r = -0.4, P = 0.08), but not in obese, participants. There was no significant difference in gastric emptying or CCK between participants who reduced their energy intake and those who did not. In conclusion, the plasma tryptophan/LNAA ratio appears to be a determinant of the suppression of energy intake in response to tryptophan in normal-weight people, but not in those with obesity. The role of the plasma tryptophan/LNAA ratio to regulate energy intake, and potential changes in obesity, warrant evaluation in prospective studies.

Effects of L-Phenylalanine on Energy Intake and Glycaemia-Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males.

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g ('Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = -0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = -0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

Physical activity is associated with accelerated gastric emptying and increased ghrelin in obesity.

BACKGROUND: Rapid gastric emptying, increased food intake, and alterations in gastrointestinal hormones are associated with obesity. The effect of regular physical activity (PA) on food intake, gastric emptying (GE), gastric accommodation, and gastrointestinal (GI) hormones in adults with obesity remains unclear. Our aim was to compare, at time of presentation, weight trends, eating behavior, GE, and GI hormone levels among individuals with obesity who engage in regular PA compared to those who do not. METHODS: In 270 participants with obesity, we performed validated measurements of GI phenotypes: GE of solids and liquids, gastric volume (GV) during fasting and after consumption of 200 mL Ensure®, satiety by kcal intake (T-kcal) during a buffet meal, satiation (volume to fullness [VTF] and maximal tolerated volume [MTV]) of a liquid nutrient, and plasma levels of fasting and postprandial GLP-1, PYY, CCK, and ghrelin. Physical Activity Stages of Change Questionnaire was used to assess whether participants were regularly PA or not. KEY RESULTS: PA was associated with lower BMI (Δ 2.01 kg/m2 , P = .001) and body weight (Δ 4.42 kg, P = .0278). GE of solids (T-50% Δ 7.54 min, P = .021) and liquids (T-50% Δ 2.99 min, P = .029%) was significantly more rapid in physically active participants. PA was also associated with relatively higher postprandial ghrelin AUC (Δ 10.4 pg/mL, P = .015). There was no significant difference in postprandial satiation, satiety, GV, or other GI hormones (CCK, PYY, or GLP-1) between groups. CONCLUSIONS & INFERENCES: Physical activity is associated with lower BMI, but faster GE and higher postprandial ghrelin levels, two factors that are also associated with obesity.

Gastrointestinal peptides in children before and after hematopoietic stem cell transplantation.

BACKGROUND: Gastrointestinal tract function and it's integrity are controlled by a number of peptides whose secretion is influenced by severe inflammation. In stomach the main regulatory peptide is ghrelin. For upper small intestine cholecystokinin and lower small intestine glucagon-like peptide- 1 are secreted, while fibroblast growth factor-21 is secreted by several organs, including the liver, pancreas, and adipose tissue [12]. Hematopoietic stem cell transplantation causes serious mucosal damage, which can reflect on this peptides. METHODS: The aim of the study was to determine fasting plasma concentrations of ghrelin, cholecystokinin, glucagon- like peptide-1, and fibroblast growth factor-21, and their gene expressions, before and 6 months after hematopoietic stem cell transplantation.27 children were studied, control group included 26 healthy children. RESULTS: Acute graft versus host disease was diagnosed in 11 patients (41%, n = 27). Median pre-transplantation concentrations of gastrointestinal peptides, as well as their gene expressions, were significantly lower in studied group compared with the control group. Only median of fibroblast growth factor-21 concentration was near-significantly higher before stem cell transplantation than in the control group. The post-hematopoietic transplant results revealed significantly higher concentrations of the studied peptides (except fibroblast growth factor-21) and respective gene expressions as compare to pre transplant results. Median glucagone like peptide-1 concentrations were significantly decreased in patients with features of acute graft versus host disease. Moreover, negative correlation between glucagone like peptide-1 concentrations and acute graft versus host disease severity was found. CONCLUSIONS: Increased concentrations and gene expressions of gastrointestinal tract regulation peptides can be caused by stimulation of regeneration in the severe injured organ. Measurement of these parameters may be a useful method of assessment of severity of gastrointestinal tract complications of hematopoietic stem cell transplantation.

Changes in the Homeostatic Appetite System After Weight Loss Reflect a Normalization Toward a Lower Body Weight.

OBJECTIVE: To compare appetite markers in reduced-obese individuals with a nonobese control group. METHODS: A total of 34 adults with obesity who lost 17% body weight at week 13 and maintained this weight loss (WL) at 1 year were compared with 33 nonobese controls matched for body composition. Basal and postprandial subjective appetite ratings and appetite-related hormone concentrations (ghrelin, total peptide YY, peptide YY3-36, total and active glucagon-like peptide 1, and cholecystokinin) were measured in all participants and repeated at week 13 and 1 year in the weight-reduced group. RESULTS: WL led to a reduction in prospective food consumption and an increase in feelings of hunger, fullness, and ghrelin secretion (basal and postprandial), but these new ratings were no different from those seen in controls. Postprandial concentrations of active glucagon-like peptide 1, total peptide YY, and cholecystokinin were lower in individuals with obesity at all time points compared with controls. CONCLUSION: The increased drive to eat (both subjective feelings of hunger and ghrelin concentrations) seen in reduced-obese individuals, both after acute and sustained WL, reflects a normalization toward a lower body weight. Overall, WL does not have a sustained negative impact on satiety peptide secretion, despite a blunted secretion in individuals with obesity compared with nonobese controls.

The effect of acute intragastric vs. intravenous alcohol administration on inflammation markers, blood lipids and gallbladder motility in healthy men.

Ethanol intake increases plasma concentrations of triglycerides and chronic ethanol use impairs lipid metabolism and causes chronic inflammation. The gut plays an important role in metabolic handling of nutrients, including lipids, and a leaky gut associated with alcohol intake, allowing inflammatory signals to the portal vein, has been proposed to constitute a mechanism by which ethanol induces hepatic inflammation. We compared the effects of enteral and parenteral administration of ethanol on a range of circulating inflammation markers (including soluble CD163, a marker of liver macrophage activation), lipids, cholecystokinin (CCK) and fibroblast growth factor 19 (FGF19) as well as gallbladder volume. On two separate and randomized study days, we subjected healthy men (n = 12) to double-blinded intragastric ethanol infusion (IGEI) and isoethanolemic intravenous ethanol infusion (IVEI). Blood was sampled and ultrasonographic evaluation of gallbladder volume was performed at frequent intervals for 4 h after initiation of ethanol administration on both days. Little or no effects were observed on plasma levels of inflammation markers during IGEI and IVEI, respectively. Circulating levels of total, low-density lipoprotein and high-density lipoprotein cholesterol decreased after ethanol administration independently of the administration form. Triglyceride and very low-density lipoprotein (VLDL) cholesterol concentrations increased more after IGEI compared to IVEI. IVEI had no effect on plasma CCK and caused an increased gallbladder volume whereas IGEI elicited a CCK response (P < 0.0001) without affecting gallbladder volume. Circulating FGF19 concentrations decreased equally in response to both ethanol administration forms. In conclusion, by evaluating a range of circulating inflammation markers during IGEI and IVEI we were not able to detect signs of systemic low-grade inflammation originating from the presence of ethanol in the gut. IVEI increased gallbladder volume whereas IGEI increased plasma CCK (with neutral effect on gallbladder volume), increased plasma VLDL cholesterol and triglyceride concentrations; indicating that the enteral route of administration may influence ethanol's effects on lipid metabolism.

Effects of intraduodenal coadministration of lauric acid and leucine on gut motility, plasma cholecystokinin, and energy intake in healthy men.

The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P < 0.05). C12+Leu and C12 reduced energy intake (P < 0.05), and there was a trend for Leu to reduce (P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.

Measurement of cholecystokinin in plasma with reference to nutrition related obesity studies.

This review describes the premises for accurate measurement of the gut hormone and satiety factor cholecystokinin (CCK) in circulation. Such a description is useful for nutrition and obesity research in which CCK in its satiety role has evoked considerable interest during the last decades. The background for the review is two sorts of considerations or concerns. First, CCK is a complex peptide system that in several ways challenges plasma measurements because the concentrations in plasma are very low (in the femtomolar to low picomolar range), and the bioactive CCK circulates in different molecular forms (CCK-58, -33, -22, and -8). Furthermore, there are major specificity problems because the structurally similar gastrin hormone circulates in 10- to 20-fold higher concentrations, and in addition, plasma proteins may, due to their high concentration, interfere in an unspecific way with immunoassay measurements. The second concern is that several obesity studies in recent decades have been based on commercial CCK kits with often inadequate documentation of the reliability in plasma measurement. Consequently, many plasma CCK results in today's obesity studies are difficult to compare. Moreover, the use of even fairly reliable commercial CCK kits has recently suffered from sudden discontinuation of the kit production, which has endangered several projects in nutrition and obesity research.

Gastrointestinal peptides and small-bowel hypomotility are possible causes for fasting and postprandial symptoms in active Crohn's disease.

BACKGROUND: Crohn's disease (CD) patients suffer postprandial aversive symptoms, which can lead to anorexia and malnutrition. Changes in the regulation of gut hormones and gut dysmotility are believed to play a role. OBJECTIVES: This study aimed to investigate small-bowel motility and gut peptide responses to a standard test meal in CD by using MRI. METHODS: We studied 15 CD patients with active disease (age 36 ± 3 y; BMI 26 ± 1 kg/m 2) and 20 healthy volunteers (HVs; age 31 ± 3 years; BMI 24 ± 1 kg/m 2). They underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling following a 400-g soup meal (204 kcal). Small-bowel motility, other MRI parameters, and glucagon-like peptide-1 (GLP-1), polypeptide YY (PYY), and cholecystokinin peptides were measured. Data are presented as means ± SEMs. RESULTS: HVs had significantly higher fasting motility indexes [106 ± 13 arbitrary units (a.u.)], compared with CD participants (70 ± 8 a.u.; P ≤ 0.05). Postprandial small-bowel water content showed a significant time by group interaction (P < 0.05), with CD participants showing higher levels from 210 min postprandially. Fasting concentrations of GLP-1 and PYY were significantly greater in CD participants, compared with HVs [GLP-1, CD 50 ± 8 µg/mL versus HV 13 ± 3 µg/mL (P ≤ 0.0001); PYY, CD 236 ± 16 pg/mL versus HV 118 ± 12 pg/mL (P ≤ 0.0001)]. The meal challenge induced a significant postprandial increase in aversive symptom scores (fullness, distention, bloating, abdominal pain, and sickness) in CD participants compared with HVs (P ≤ 0.05). CONCLUSIONS: The decrease in fasting small-bowel motility noted in CD participants can be ascribed to the increased fasting gut peptides. A better understanding of the etiology of aversive symptoms in CD will facilitate identification of better therapeutic targets to improve nutritional status. This trial was registered at clinicaltrials.gov as NCT03052465.