Plasma Cholecystokinin Concentrations Research Articles

High Fat Diets Increase Plasma Cholecystokinin and Pancreatic Polypeptide, and Decrease Plasma Insulin and Feed Intake in Lactating Cows

High fat diets often decrease feed intake in dairy cows; however, mechanisms underlying fat-induced depression of feed intake are yet to be established. The postulate that high fat diets decrease feed intake by increasing concentrations of lipid metabolites or satiety hormones in blood was tested by using eight multiparous Holstein cows in a simultaneously replicated 4 × 4 Latin-square design. Treatments were control diet with 1) no fat added, 2) 30 g/kg calcium salts of long-chain fatty acids, 3) 60 g/kg calcium salts of long-chain fatty acids, and 4) 90 g/kg calcium salts of long-chain fatty acids. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage and alfalfa hay (50:25:14:11 on a dry matter basis). Dry matter and energy intakes were decreased by inclusion of calcium salts of long-chain fatty acids >30 g/kg of total diet dry matter (P = 0.0001). Plasma nonesterified fatty acids and triglyceride concentrations were increased linearly by feeding increasing amounts of fat (P < 0.003 and P = 0.0001, respectively), whereas plasma β-hydroxybutyrate and glucose concentrations were not influenced by supplemental fat. Fat supplementation increased postfeeding plasma cholecystokinin concentrations and linearly increased plasma pancreatic polypeptide concentrations. Highest concentrations of plasma cholecystokinin (P < 0.001) and pancreatic polypeptide (P < 0.05) were observed in cows fed the 90 g/kg fat supplement. Plasma insulin was lowered linearly by feeding fat (P = 0.0001). Increased concentrations of cholecystokinin and pancreatic polypeptide were associated with decreased intakes of feed and energy, whereas insulin may not be involved in the control of feed intake in cows fed fat.

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.

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.

Tailoring Emulsions for Controlled Lipid Release: Establishing in vitro-in Vivo Correlation for Digestion of Lipids.

The use of oil-in-water emulsions for controlled lipid release is of interest to the pharmaceutical industry in the development of poorly water soluble drugs and also has gained major interest in the treatment of obesity. In this study, we focus on the relevant in vitro parameters reflecting gastric and intestinal digestion steps to reach a reliable in vitro-in vivo correlation for lipid delivery systems. We found that (i) gastric lipolysis determines early lipid release and sensing. This was mainly influenced by the emulsion stabilization mechanism. (ii) Gastric mucin influences the structure of charge-stabilized emulsion systems in the stomach, leading to destabilization or gel formation, which is supported by in vivo magnetic resonance imaging in healthy volunteers. (iii) The precursor structures of these emulsions modulate intestinal lipolysis kinetics in vitro, which is reflected in plasma triglyceride and cholecystokinin concentrations in vivo.

Development of small intestinal enzyme activities and their relationship with some gut regulatory peptides in grazing sheep

Growth depends on an animal's capacity to digest and assimilate ingested nutrients, and insufficient supply and impairment will constrain lamb growth. Eight groups of Alpine Finewool lambs were harvested on 0, 3, 7, 14, 21, 28, 42, and 56 d to measure pH and enzymatic activities in the duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum mucosa or digesta. From the duodenum to the ileum the pH of intestinal mucosa and digesta increased, whereas pH changed very little with age. The trypsin, chymotrypsin, lipase, lactase, and α-amylase activities observed at birth decreased by d 3, followed by a nonuniform enzymatic response in the small intestine. The trypsin activity increased from d 3 to peak, at d 21, followed by a decline. Chymotrypsin activity followed the same general trend but with smaller responses in activities. Trypsin demonstrated greater enzymatic activity than chymotrypsin at the same age. The lipase activity of small intestinal mucosa and digesta changed little with age. The lactase activity was high at birth, decreased by d 3, and then increased, followed by a decrease as lambs approached weaning. α-Amylase activity was similar in the small intestinal mucosa and digesta at birth but increased with age for the duodenum and proximal jejunum. Plasma concentrations of cholecystokinin (CCK), secretin, and gastrin were positively correlated ( < 0.05) with ileal mucosa lipase activity. Plasma concentration of CCK, secretin, gastrin, and gastric inhibitory polypeptide (GIP) were positively correlated ( < 0.05) with ileal mucosa lactase activity. Plasma concentration of pancreatic polypeptide (PP) was negatively correlated ( < 0.05) with lactase activity in the middle jejunum and ileal mucosa. Plasma concentrations of CCK, secretin, gastrin, and GIP were positively correlated ( < 0.05) with α-amylase activity in the ileal mucosa but negatively correlated ( < 0.05) with duodenum, prejejunum, and middle jejunum. Plasma PP concentrations were positively correlated ( < 0.01) with α-amylase activity of duodenum, middle jejunum, and postjejunum mucosa but not with the enzyme activity of postjejunum and ileal mucosa ( > 0.05). Small intestinal enzymatic activities exist and may be sufficient to enhance lamb growth via appropriate nutrient supplementation.

Mechanism-Based Modeling of Gastric Emptying Rate and Gallbladder Emptying in Response to Caloric Intake.

Bile acids released postprandially modify the rate and extent of absorption of lipophilic compounds. The present study aimed to predict gastric emptying (GE) rate and gallbladder emptying (GBE) patterns in response to caloric intake. A mechanism‐based model for GE, cholecystokinin plasma concentrations, and GBE was developed on data from 33 patients with type 2 diabetes and 33 matched nondiabetic individuals who were administered various test drinks. A feedback action of the caloric content entering the proximal small intestine was identified for the rate of GE. The cholecystokinin concentrations were not predictive of GBE, and an alternative model linking the nutrients amount in the upper intestine to GBE was preferred. Relative to fats, the potency on GBE was 68% for proteins and 2.3% for carbohydrates. The model predictions were robust across a broad range of nutritional content and may potentially be used to predict postprandial changes in drug absorption.

Prior Consumption of a Fat Meal in Healthy Adults Modulates the Brain’s Response to Fat

Background: The consumption of fat is regulated by reward and homeostatic pathways, but no studies to our knowledge have examined the role of high-fat meal (HFM) intake on subsequent brain activation to oral stimuli.Objective: We evaluated how prior consumption of an HFM or water load (WL) modulates reward, homeostatic, and taste brain responses to the subsequent delivery of oral fat.Methods: A randomized 2-way crossover design spaced 1 wk apart was used to compare the prior consumption of a 250-mL HFM (520 kcal) [rapeseed oil (440 kcal), emulsifier, sucrose, flavor cocktail] or noncaloric WL on brain activation to the delivery of repeated trials of a flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 men) aged 25 ± 2 y and with a body mass index (in kg/m2) of 22.4 ± 0.8. We tested differences in brain activation to the CS and FS and baseline cerebral blood flow (CBF) after the HFM and WL. We also tested correlations between an individual’s plasma cholecystokinin (CCK) concentration after the HFM and blood oxygenation level–dependent (BOLD) activation of brain regions.Results: Compared to the WL, consuming the HFM led to decreased anterior insula taste activation in response to both the CS (36.3%; P < 0.05) and FS (26.5%; P < 0.05). The HFM caused reduced amygdala activation (25.1%; P < 0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula: 5.7%; P < 0.01), homeostatic (hypothalamus: 9.2%, P < 0.01; thalamus: 5.1%, P < 0.05), and reward areas (striatum: 9.2%; P < 0.01) after the HFM. An individual’s plasma CCK concentration correlated negatively with brain activation in taste and oral somatosensory (ρ = −0.39; P < 0.05) and reward areas (ρ = −0.36; P < 0.05).Conclusions: Our results in healthy adults show that an HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain’s response to high-fat counterparts and guide future interventions to reduce obesity.

Contributions of upper gut hormones and motility to the energy intake-suppressant effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis.

We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed‐effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within‐subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon‐like peptide‐1 (GLP‐1) and time‐to‐peak GLP‐1 concentrations, GLP‐1 AUC and bloating scores (P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake (P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative contributions from a range of interrelated factors.

Critical review evaluating the pig as a model for human nutritional physiology.

The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet), glutamic acid (umami) and fatty acids are conserved between humans and pigs. In contrast, pigs show limited perception of high-intensity sweeteners and NaCl and sense a wider array of amino acids than humans. Differences on bitter taste may reflect the adaptation to ecosystems. In relation to appetite regulation, plasma concentrations of cholecystokinin and glucagon-like peptide-1 are similar in pigs and humans, while peptide YY in pigs is ten to twenty times higher and ghrelin two to five times lower than in humans. Pigs are an excellent model for human studies for vagal nerve function related to the hormonal regulation of food intake. Similarly, the study of gut barrier functions reveals conserved defence mechanisms between the two species particularly in functional permeability. However, human data are scant for some of the defence systems and nutritional programming. The pig model has been valuable for studying the changes in human microbiota following nutritional interventions. In particular, the use of human flora-associated pigs is a useful model for infants, but the long-term stability of the implanted human microbiota in pigs remains to be investigated. The similarity of the pig and human brain anatomy and development is paradigmatic. Brain explorations and therapies described in pig, when compared with available human data, highlight their value in nutritional neuroscience, particularly regarding functional neuroimaging techniques.

Duodenal fatty acid sensor and transporter expression following acute fat exposure in healthy lean humans

Free fatty acids (FFAs) and their derivatives are detected by G-protein coupled receptors (GPRs) on enteroendocrine cells, with specific transporters on enterocytes. It is unknown whether acute fat exposure affects FFA sensors/transporters, and whether this relates to hormone secretion and habitual fat intake. We studied 20 healthy participants (10M, 10F; BMI: 22±1kg/m2; age: 28±2 years), after an overnight fast, on 2 separate days. On the first day, duodenal biopsies were collected endoscopically before, and after, a 30-min intraduodenal (ID) infusion of 10% Intralipid®, and relative transcript expression of FFA receptor 1 (FFAR1), FFA receptor 4 (FFAR4), GPR119 and the FFA transporter, cluster of differentiation-36 (CD36) was quantified from biopsies. On the second day, ID Intralipid® was infused for 120-min, and plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) evaluated. Habitual dietary intake was assessed using food frequency questionnaires (FFQs). ID Intralipid® increased expression of GPR119, but not FFAR1, FFAR4 and CD36, and stimulated CCK and GLP-1 secretion. Habitual polyunsaturated fatty acid (PUFA) consumption was negatively associated with basal GPR119 expression. GPR119 is an early transcriptional responder to duodenal lipid in lean humans, although this response appeared reduced in individuals with high PUFA intake. These observations may have implications for downstream regulation of gut hormone secretion and appetite. This study was registered as a clinical trial with the Australia and New Zealand Clinical Trial Registry (Trial number: ACTRN12612000376842).

Effects of Intraduodenal Infusions of L-phenylalanine and L-glutamine on Antropyloroduodenal Motility and Plasma Cholecystokinin in Healthy Men.

Background/AimsDietary proteins have potent eating-inhibitory and glucose-lowering effects, which may be mediated via effects of amino acids on gastrointestinal hormone and motor function, although little information is available. We have now evaluated the effects of L-phenylalanine (L-Phe) and L-glutamine (L-Gln) on antropyloroduodenal motility and plasma cholecystokinin (CCK) concentrations.MethodsTwo double-blind, 3-way cross-over studies were performed, each including 10 healthy, normal-weight men. We determined the antropyloroduodenal motor and plasma CCK responses to 90-minute intraduodenal infusions of L-Phe (study A) or L-Gln (study B), each at 0.15 kcal/min (total 13.5 kcal), or 0.45 kcal/min (total 40.5 kcal), or saline (control), in randomized fashion.ResultsIntraduodenal L-Phe at 0.45 kcal/min, but not at 0.15 kcal/min, suppressed antral (P < 0.01), and stimulated phasic (P < 0.01), but not tonic, pyloric, or duodenal pressures, while L-Phe at both 0.15 kcal/min and 0.45 kcal/min stimulated plasma CCK. In contrast, L-Gln had no effect on antral, duodenal or pyloric pressures, or plasma CCK.ConclusionsIntraduodenal infusions of L-Phe and L-Gln, in doses of 0.15 kcal/min and 0.45 kcal/min for 90 minutes, have different effects on antropyloroduodenal motility and CCK in normal-weight men. The modulation of antral and pyloric pressures and CCK may contribute to the eating-inhibitory effects of oral L-Phe, possibly through the slowing of gastric emptying.

Dietary thylakoids suppress blood glucose and modulate appetite-regulating hormones in pigs exposed to oral glucose tolerance test

Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet. Six pigs were fed a high fat diet (36 energy% fat) for one month before oral glucose tolerance test (1g/kg d-glucose) was performed. The experiment was designed as a cross-over study, either with or without addition of 0.5g/kg body weight of thylakoid powder. The supplementation of thylakoids to the oral glucose tolerance test resulted in decreased blood glucose concentrations during the first hour, increased plasma cholecystokinin concentrations during the first two hours, and decreased late postprandial secretion of ghrelin. Dietary thylakoids may be a novel agent in reducing the glycaemic responses to high carbohydrate and high glycaemic index foods. Thylakoids may in the future be promising for treatment and prevention of diabetes, overweight and obesity.

Gastric Lipase Secretion in Children with Gastritis

Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005) and the control group (p < 0.005). Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003) and the HPG group (p < 0.01). We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

Human chorionic gonadotropin regulates gastric emptying in ovariectomized rats

Prolongation of gastrointestinal transit resulting in nausea and vomiting in pregnancy (NVP) is the most common phenomenon during the first trimester of pregnancy. Increased human chorionic gonadotropin (hCG) concentration during the first trimester is the most likely cause of NVP. The aim of this study was to investigate the effect of hCG on gastrointestinal transit and plasma concentrations of cholecystokinin (CCK) in ovariectomized (Ovx) rats. I.p. injection of hCG was used to evaluate the dose effect of hCG on gastrointestinal transit in Ovx rats. The CCK antagonist lorglumide was used to clarify the role of CCK in regulating gastrointestinal transit. Gastrointestinal transit was assessed 15 min after intragastric gavage of a mixture of 10% charcoal and Na(2)(51)CrO(4) (0.5 μCi/ml). After i.p. administration of hCG, gastric emptying was inhibited in Ovx rats, but intestinal transit was not affected. Plasma CCK concentrations were increased in a dose-dependent manner after hCG treatment, and gastric emptying showed a significant negative correlation with CCK concentrations (P=0.01, r(2)=-0.5104). Peripheral administration (i.p.) of lorglumide, a selective CCK(1) receptor antagonist, attenuated the hCG-induced inhibition of gastric emptying in Ovx rats, whereas central administration via the i.c.v. route did not. hCG treatment of Ovx rats inhibits gastric emptying in a dose-dependent manner via a peripheral mechanism of CCK hypersecretion and activation of CCK(1) receptors.

Increasing the number of masticatory cycles is associated with reduced appetite and altered postprandial plasma concentrations of gut hormones, insulin and glucose

To determine the influence of masticatory efficiency on postprandial satiety and glycaemic response, twenty-one healthy males were recruited for this randomised cross-over trial. The participants consumed a fixed amount of pizza provided in equal-sized portions by chewing each portion either fifteen or forty times before swallowing. Subjective appetite was measured by appetite questionnaires at regular intervals for 3 h after the meal and plasma samples were collected for the measurement of selected satiety-related hormones, glucose, insulin and glucose-dependent insulinotropic peptide (GIP) concentrations. An ad libitum meal was provided shortly after the last blood sample was drawn and the amount eaten recorded. Compared with fifteen chews, chewing forty times per portion resulted in lower hunger (P= 0·009), preoccupation with food (P= 0·005) and desire to eat (P= 0·002). Meanwhile, plasma concentrations of glucose (P= 0·024), insulin (P< 0·001) and GIP (P< 0·001) were higher following the forty-chews meal. Chewing forty times before swallowing also resulted in a higher plasma cholecystokinin concentration (P= 0·045) and a trend towards a lower ghrelin concentration (P= 0·051). However, food intake at the subsequent test meal did not differ (P= 0·851). The results suggest that a higher number of masticatory cycles before swallowing may provide beneficial effects on satiety and facilitate glucose absorption.

Disturbed eating at high altitude: influence of food preferences, acute mountain sickness and satiation hormones

Hypoxia has been shown to reduce energy intake and lead to weight loss, but the underlying mechanisms are unclear. The aim was therefore to assess changes in eating after rapid ascent to 4,559 m and to investigate to what extent hypoxia, acute mountain sickness (AMS), food preferences and satiation hormones influence eating behavior. Participants (n = 23) were studied at near sea level (Zurich (ZH), 446 m) and on two days after rapid ascent to Capanna Margherita (MG) at 4,559 m (MG2 and MG4). Changes in appetite, food preferences and energy intake in an ad libitum meal were assessed. Plasma concentrations of cholecystokinin, peptide tyrosine-tyrosine, gastrin, glucagon and amylin were measured. Peripheral oxygen saturation (SpO(2)) was monitored, and AMS assessed using the Lake Louis score. Energy intake from the ad libitum meal was reduced on MG2 compared to ZH (643 ± 308 vs. 952 ± 458 kcal, p = 0.001), but was similar to ZH on MG4 (890 ± 298 kcal). Energy intake on all test days was correlated with hunger/satiety scores prior to the meal and AMS scores on MG2 but not with SpO(2) on any of the 3 days. Liking for high-fat foods before a meal predicted subsequent energy intake on all days. None of the satiation hormones showed significant differences between the 3 days. Reduced energy intake after rapid ascent to high altitude is associated with AMS severity. This effect was not directly associated with hypoxia or changes in gastrointestinal hormones. Other peripheral and central factors appear to reduce food intake at high altitude.

Blocking opioid receptors alters short-term feed intake and oro-sensorial preferences in weaned calves

Opioid peptides may participate in the control of feed intake through mechanisms involving pleasure reward linked to consumption of palatable feed. The objective of this study was to determine whether blocking opioid receptors might void oro-sensorial preferences of calves, and affect circulating glucose, insulin, and anorexigenic hormones in fasted and fed calves. Two experiments involved 32 Holstein calves [body weight (BW)=86.5±1.73kg, age=72±0.6 d]. In experiment 1, all calves received an ad libitum choice of the same feed either unflavored or flavored with a sweetener (Luctarom SFS-R, Lucta, Montornès del Vallès, Spain). Feed consumption was recorded every 2h from 0800 to 1400h for 3 consecutive days to verify the establishment of an oro-sensorial preference for sweet feed (SF). The SF was preferred over the control feed (CF) at all recorded times. In experiment 2, calves were subjected to a 2 × 2 factorial design to study the interaction between opioid activity and metabolic state. Half of the calves were fasted for 14h (FAS), whereas the other half remained well fed (FED). Within each of these groups, at feeding time (0800h), half of the calves received an i.v. injection of naloxone (NAL, an opioid receptor antagonist; 1mg/kg of BW) and the other half was injected with saline solution (SAL; 0.9% NaCl). Therefore, treatments were FED-NAL, FED-SAL, FAS-NAL, and FAS-SAL. Blood samples were taken at −10, 20, 180, and 240min relative to NAL or SAL injections. As expected, cumulative consumption of starter feed was greater in FAS than in FED calves. Total feed consumption 2h after feeding was lower in NAL than in SAL calves. Calves in the FAS group did not discern between CF and SF during the first 4h after feed offer. Preference for SF was greater in SAL than in NAL calves. Calves in the FED-SAL treatment preferred SF at 2 and 6h after feed offer and tended to prefer SF at 4h after feeding. However, FED-NAL calves did not discern between SF and CF during the first 4h after feeding and tended to prefer SF only after 6h from feeding. Plasma glucose, insulin, and cholecystokinin concentrations were greater in FED than in FAS calves. Injection of naloxone decreased plasma glucagon-like peptide-1 (GLP-1) in NAL calves. Blocking opioid receptors reduced intake the first 2h after naloxone injection in FED calves, altered oro-sensorial preferences, and reduced plasma GLP-1 concentration. In conclusion, the opioid peptide system may control short-term feed intake by modulating the oro-sensorial response triggered by feed consumption, especially when calves are fed ad libitum.

Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations

Gastrointestinal (GI) motility and gut hormones have been considered to be involved in the development and maintenance of obesity. Our aim was to assess the relationships between gastric emptying (GE), GI transit and gut hormones and leptin concentrations in diet-induced obese rat model. Male 6-week-old Sprague–Dawley rats were fed with a high-fat (HF) diet for 8weeks to generate diet-induced obesity (DIO) and diet resistant (DR) rats. GE, GI transit and plasma ghrelin, cholecystokinin (CCK), PYY and leptin concentrations were determined in DIO, DR and control (CON) rats. The DIO rats had slower GE, higher plasma leptin and CCK concentrations, and lower plasma ghrelin concentration compared with CON and DR rats. GE was correlated with plasma ghrelin (r=0.402, P=0.028), CCK (r=−0.518, P=0.003) and leptin concentration (r=−0.514, P=0.004). The slower GE, which can be considered as an adaptive response aimed at HF diet induced obesity, may be mediated by changes of plasma ghrelin, CCK and leptin concentrations.

Aging and Peptide Control of Food Intake

Aging affects energy homeostasis and fuel metabolism in a form of either an increased body mass and glucose intolerance that may lead to obesity and type 2 diabetes or loss of appetite that also may seriously compromise health status. The data, obtained mainly in rat, suggest that aging suppresses the expression and action of potent orexigenic peptides such as predominantly neuropeptides NPY and orexins as peripheral hormone, ghrelin. Senescent animals show over-responsiveness to αMSH, the major anorexigenic neuropeptide. However, central anorexigenic action of leptin is clearly diminished in aging, most likely due to the impaired leptin signal transduction. The age-related central resistance to leptin and insulin does not reduce their inhibitory effects on the activity of NPY and AgRP neurons. Thus, in rodents aging is associated with the altered expression and activity of both orexigenic and anorexigenic peptides. If similar changes in the central regulation of food intake occur during human aging, they may partially explain 'anorexia of aging' and loss of body weight observed at the end-of-life period. Additionally, increased plasma cholecystokinin concentrations in healthy old subjects may also contribute to the loss of appetite characteristic for the elderly. Further studies of the central and peripheral mechanisms that control food intake during aging may provide novel therapeutic strategies to improve the nutritional status of the elderly.

Effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese and diet-resistant rats

Gut hormones play key roles in the regulation of energy homeostasis. However, little is known about the long- and short-term effects of changing dietary fat content on gut hormones. We aim to examine the effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese (DIO) and diet-resistant (DR) rats. After inducing obesity with a high-fat (HF) diet, male Sprague-Dawley rats were divided into three groups according to their body-weight gain: DIO; DR; control (CON). The DIO and DR rats were further divided in random into two groups. One continued on a HF diet and the other switched to a low-fat (LF) diet for an additional 4 weeks. Finally, each group was randomly divided into three subgroups (n 8): fasted; fasted-refed HF; fasted-refed LF diet groups. Replacing a HF diet with a LF diet for 4 weeks resulted in less fat mass, higher fasting and post-HF plasma ghrelin concentration and lower postprandial plasma cholecystokinin concentration in the DIO and DR rats. Acute switching dietary fat resulted in significantly higher post-HF plasma ghrelin concentrations than post-LF ghrelin concentrations in the DR rats on LF diet (DRLF) and DIO rats on LF diet (DIOLF) rats, and significantly higher post-HF obestatin concentrations than post-LF obestatin concentrations in the CON, DR rats on HF diet (DRHF) and DRLF rats. Dietary fat content appears to play a role in the gut hormone profile, which may consequently influence fat mass.