Acute Feeding Studies Research Articles

Effects of Protein Source and Quantity on Appetite Control, Satiety and Subsequent Food Intake in Healthy Adults

Abstract Objectives To examine whether consumption of breakfast preloads varying in protein source and quantity affect measures of appetite, satiety and subsequent energy intake in healthy adults. Methods Thirty-seven healthy adults (Age: 26 ± 4; BMI: 23 ± 2) participated in this randomized crossover design study. On 3 consecutive days, participants consumed 325 kcal preload breakfast yogurts, varying in protein quality (Whey vs. Pea) and quantity (20, 30, 40 g) vs. an isocaloric carbohydrate preload (Control). On day 4, participants completed a 5-hr in clinic testing day. At baseline time -15 min, questionnaires assessing hunger, fullness, desire to eat, prospective food consumption, and eating initiation, were completed. At time 0 min, the respective preload was provided, and palatability assessed. At time 15 min, after consumption, similar questionnaires were completed every 30 min during the 4-h postprandial period followed by an ad libitum pizza lunch. There was a 3–7 day washout period between testing days. To assess main effects of protein source, paired sample t-tests of incremental area under the curve (iAUC) were computed for 20g Pea vs. 20g Whey preloads on 4-h hunger, fullness, desire to eat, prospective food consumption, eating initiation and lunch energy intake. To assess main effects of protein quantity, repeated measures ANOVA was computed between control and pea protein preloads of 20g, 30g, and 40g on 4-h hunger, fullness, desire to eat, and prospective food consumption niAUC, eating initiation, and lunch energy intake. P < 0.05 was considered statistically significant. Statistical analyses were performed using The R Foundation (R; version 4.0.3). Results No main effects of protein source or quantities were detected for 4-h postprandial hunger, fullness, desire to eat, and prospective food consumption niAUC. On average, participants requested to eat again 2-h after breakfast (134 ± 12 min) and consumed on average 830 ± 10 kcals at lunch with no differences between protein sources or quantities. Conclusions In the context of an acute feeding study, no differences in postprandial appetite, satiety, and subsequent food intake were detected when comparing protein preloads varying in source and quantity. These data suggest that 20 g pea protein is sufficient to elicit satiety effects and can be used as a plant-based alternative for whey protein. Funding Sources Roquette.

A high-protein meal does not improve blood pressure or vasoactive biomarker responses to acute exercise in humans

Blood pressure (BP) responses to exercise yield prognostic information beyond resting BP. While habitual higher dietary protein intake is associated with reduced resting BP, few studies have assessed the impact of high-protein meals on acute BP and vasoactive biomarker responses to exercise. To test the hypothesis that consuming a higher-protein, lower fat meal (HP; 30 g protein, 17 g fat, 52 g carbohydrate) would attenuate the BP response to exercise and result in a more robust post-exercise hypotensive response compared to a lower-protein, higher-fat meal (LP; 13 g protein, 25 g fat, 54 g carbohydrate), we recruited 31 pre-hypertensive subjects to complete this randomized, double-blind, cross-over acute feeding study. One hundred sixty-five minutes after consuming the test HP or LP meal, subjects exercised on a cycle ergometer at 70% VO2 max for 30 minutes. Blood pressure was measured prior to the meal and periodically before, during, and after exercise for a 315-minute period. Blood samples were periodically collected to quantify plasma arginine, arginine metabolites (asymmetric dimethylarginine, symmetric dimethylarginine; ADMA, SDMA), endothelin-1, nitrates, and nitrites in a subset of subjects (n = 15) as shown in Supplemental Table S1. Consuming the HP meal did not influence the BP responses to exercise, including the post-exercise return to baseline BP or systolic BP area under the curve. While the HP meal resulted in greater postprandial plasma arginine concentrations, ADMA, SDMA, endothelin-1, nitrates, and nitrites were unaltered. These results suggest that consuming a higher-protein, lower-fat meal does not influence BP or vasoactive biomarker responses to exercise compared to a lower-protein, higher-fat meal.

Consuming decaffeinated coffee with milk and sugar added before a high-glycaemic index meal improves postprandial glycaemic and insulinaemic responses in healthy adults.

The present study aimed to compare the effects of drinking different types of coffee before a high-glycaemic index (GI) meal on postprandial glucose metabolism and to assess the effects of adding milk and sugar into coffee. In this randomised, crossover, acute feeding study, apparently healthy adults (n 21) consumed the test drink followed by a high-GI meal in each session. Different types of coffee (espresso, instant, boiled and decaffeinated, all with milk and sugar) and plain water were tested in separate sessions, while a subset of the participants (n 10) completed extra sessions using black coffees. Postprandial levels of glucose, insulin, active glucagon-like peptide 1 (GLP-1) and nitrotyrosine between different test drinks were compared using linear mixed models. Results showed that only preloading decaffeinated coffee with milk and sugar led to significantly lower glucose incremental AUC (iAUC; 14 % lower, P = 0·001) than water. Preloading black coffees led to greater postprandial glucose iAUC than preloading coffees with milk and sugar added (12-35 % smaller, P < 0·05 for all coffee types). Active GLP-1 and nitrotyrosine levels were not significantly different between test drinks. To conclude, preloading decaffeinated coffee with milk and sugar led to a blunted postprandial glycaemic response after a subsequent high-GI meal, while adding milk and sugar into coffee could mitigate the impairment effect of black coffee towards postprandial glucose responses. These findings may partly explain the positive effects of coffee consumption on glucose metabolism.

Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight, and obese men.

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m2] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m2) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher (P < 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 (P = 0.06) and ceramide C16:0 (P < 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.

Consuming coffee with milk and sugar added before a high glycemic index meal improves postprandial glycemic and insulinemic responses

AbstractLiterature regarding the health effect of coffee consumption was contradicting, whereby it was found to protect against type 2 diabetes while inducing acute glucose intolerance. Previous studies suggested that adding sugar and milk into coffee may alter the effect of its consumption on glucose metabolism, potentially explaining the contradiction, but this is seldom investigated. This study aimed at assessing the effect of adding milk and sugar into coffee on the postprandial glycemic metabolism after a subsequent, high glycemic index (GI) meal. A total of 11 apparently healthy adults were recruited for this randomized, cross-over acute feeding study. In each experimental session, overnight-fasted participants consumed one cup of the following drinks: espresso (35 ml), instant, boiled, and decaffeinated coffee (all 150 ml). Then they consumed a high GI meal and blood samples were collected every 15–30 minutes in the subsequent two hours. Each type of coffee was tested for 3 times, twice with 50 g low-fat milk and 7.5 g white sugar added (i.e. white coffee) and once without (i.e. black coffee). Postprandial levels of glucose, insulin, and active GLP-1, as well as the incremental area-under-curve (iAUC) of the biomarkers, were compared between black and white coffee, with baseline measurements as a covariate. Results showed that the peak glucose level after the meal was lower in white coffee sessions than black coffee sessions, regardless of coffee types. The difference was the greatest between black and white decaffeinated coffee (mean difference from baseline ± SEM, white coffee: 2.5 ± 0.2 mmol/L; black coffee: 3.3 ± 0.3 mmol/L, p = 0.019). The mean glucose iAUC of white coffee sessions was significantly smaller than black coffee sessions for all coffee types except for instant coffee (all p &lt; 0.05). The peak insulin levels between black and white coffees were not significantly different, yet white decaffeinated coffee had a 35% smaller mean insulin iAUC than black decaffeinated coffee (p = 0.025). The active GLP-1 levels were not significantly different between black and white coffee sessions. These results showed that prior ingestion of coffee with milk and sugar added attenuated the glucose response after the subsequent meal, compared with drinking black coffee beforehand. Our results may provide an explanation for the conflicting literature regarding the protective effects of coffee consumption against type 2 diabetes.

Novel lipid side chain modified exenatide analogs emerged prolonged glucoregulatory activity and potential body weight management properties

Exenatide is known as the first marketed GLP-1 agonist for antidiabetic treatment, but it need twice injection a day because of its fast clearance. This work aims to prolong the half-life of exenatide by modified with novel lipid chain. Four optimized exenatide analogs named as Cys12-Exenatide (1–39)-NH2, Cys40-Exenatide (1–39)-NH2, Cys12-Tyr22-Gln24-Glu28-Arg35-Exenatide (1–39)-NH2 and Tyr22-Gln24-Glu28-Arg35-Cys40-Exenatide (1–39)-NH2 were selected and applied for conjugation. Then a series of evaluations including GLP-1R activation assay were conducted, conjugation C2 was selected for further investigation. Glucoregulatory and insulin secretion assay and hypoglycemic duration test were accessed and showed that C2 was capable of comparable insulinotropic activities and glucose-lowering abilities with those of liraglutide and exenatide. Cell protective effects in INS-1 cells confirmed that C2 had relatively protection effects. Meanwhile, once daily injection of C2 to STZ-induced diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. Acute feeding studies were evaluated in DIO mice. These results suggested that C2 is a promising agent for further investigation of its potential to treat diabetes patients with obese.

GLP-1 and PYY3-36 reduce high-fat food preference additively after Roux-en-Y gastric bypass in diet-induced obese rats

BackgroundRoux-en-Y gastric bypass (RYGB) modifies various aspects of eating behavior in morbidly obese individuals to cause marked and lasting weight loss and improvements in metabolic health, but the underlying mechanisms remain poorly understood. ObjectivesTo assess the relative contributions of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY3-36), whose circulating levels are enhanced by RYGB, in the reduced high-fat (HF) food preference that develops postoperatively. SettingUniversity hospital, Würzburg, Germany. MethodsHF diet–induced obese male Wistar rats underwent RYGB (n = 11) or sham (n = 7) surgeries and were subsequently maintained on a choice of low-fat (10% calories from fat) and HF (60% calories from fat) diets. From postoperative weeks 4 to 6, acute feeding studies were performed in which the selective GLP-1 receptor antagonist exendin-9 (30 μg/kg), the second-generation selective Y2 receptor antagonist JNJ-31020028 (10 mg/kg), or a combination of both drugs was administered intraperitoneally. ResultsDuring the observational period weight, adiposity and total food intake were lower while postprandial plasma GLP-1 and peptide tyrosine tyrosine levels were higher for RYGB-operated compared with sham-operated rats. There was a gradual shift in preference from HF to low-fat food in RYGB-operated rats by postoperative week 3. Single antagonist treatments had a relatively modest impact on HF food preference in rats from both surgical groups. However, dual antagonist treatment caused a striking increase in HF food preference specifically in RYGB-operated rats. ConclusionsGLP-1 and peptide tyrosine tyrosine 3-36 reduce HF food preference additively after RYGB supporting the use of gut hormone combination strategies for healthier feeding behavior.

Untargeted Metabolomics Identifies Novel Potential Biomarkers of Habitual Food Intake in a Cross-Sectional Study of Postmenopausal Women

Recent studies suggest that untargeted metabolomics is a promising tool to identify novel biomarkers of individual foods. However, few large cross-sectional studies with comprehensive data on habitual diet and circulating metabolites have been conducted. We aimed to identify potential food biomarkers and evaluate their predictive accuracy. We conducted a cross-sectional analysis of consumption of 91 food groups or items, assessed by a 152-item food-frequency questionnaire, in relation to 1186 serum metabolites measured by mass spectrometry-based platforms from 1369 nonsmoking postmenopausal women (mean age=68.3 y). Diet-metabolite associations were selected by Pearson's partial correlation analysis (P<4.63×10-7, |r|>0.2). The predictive accuracy of the selected food metabolites was evaluated from the area under the curve (AUC) calculated from receiver operating characteristic analysis conducted among women in the top and bottom quintiles of dietary intake. We identified 379 diet-metabolite associations. Forty-two food groups or items were correlated with 199 serum metabolites. We replicated 63 metabolites as biomarkers of habitual food intake reported in previous cross-sectional studies. Among those not previously shown to be associated with habitual diet, several are biologically plausible and were reported in acute feeding studies including: banana and dopamine 3-O-sulfate (r=0.34, AUC=76%) and dopamine 4-O-sulfate (r=0.33, AUC=74%), garlic and alliin (r=0.24, AUC=69%), N-acetylalliin (r=0.27, AUC=70%), and S-allylcysteine (r=0.23, AUC=69). Two unannotated metabolites were the strongest predictors for dark fish (X-02269, r=0.51, AUC=94%) and coffee intake (X-21442, r=0.62, AUC=98%). In this comprehensive, cross-sectional analysis of habitual food intake and serum metabolites among postmenopausal women, we identified several potentially novel food biomarkers and replicated others. Our findings contribute to the limited literature on food-based biomarkers and highlight the significant and promising role that large cohort studies with archived blood samples could play in this field. This study was registered at clinicaltrials.gov as NCT03282812.

Saturated fatty acids, obesity, and the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome in asthmatic patients

Both obesity and high dietary fat intake activate the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. We aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatic patients after macronutrient overload and in immune cells challenged by inflammasome triggers. Study 1 was a cross-sectional observational study of nonobese (n=51) and obese (n=76) asthmatic adults. Study 2 was a randomized, crossover, acute feeding study in 23 asthmatic adults (n=12 nonobese and n=11 obese subjects). Subjects consumed 3 isocaloric meals on 3 separate occasions (ie, saturated fatty acid, n-6 polyunsaturated fatty acid, and carbohydrate) and were assessed at 0 and 4hours. For Studies 1 and 2, airway inflammation was measured based on sputum differential cell counts, IL-1β protein levels (ELISA), and sputum cell gene expression (Nanostring nCounter). In Study 3 peripheral blood neutrophils and monocytes were isolated by using Ficoll density gradient and magnetic bead separation and incubated with or without palmitic acid, LPS, or TNF-α for 24hours, and IL-1β release was measured (ELISA). In Study 1 NLRP3 and nucleotide oligomerization domain 1 (NOD1) gene expression was upregulated, and sputum IL-1β protein levels were greater in obese versus nonobese asthmatic patients. In Study 2 the saturated fatty acid meal led to increases in sputum neutrophil percentages and sputum cell gene expression of Toll-like receptor 4 (TLR4) and NLRP3 at 4hours in nonobese asthmatic patients. In Study 3 neutrophils and monocytes released IL-1β when challenged with a combination of palmitic acid and LPS or TNF-α. The NLRP3 inflammasome is a potential therapeutic target in asthmatic patients. Behavioral interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction, warrant further exploration.

Influence of rice, pea and oat proteins in attenuating glycemic response of sugar-sweetened beverages.

Liquids have higher ingestion and gastric-emptying rates, resulting in rapid glycemic response. They are also less satiating than solid foods. This study examined if the addition of plant proteins alter postprandial glucose, insulin, triglycerides, glucose-dependent insulinotropic peptide (GIP), glycogen-like peptide-1 (GLP-1) and appetitive responses to a sugar-sweetened beverage. This was a randomized, crossover acute feeding study consisting of four treatments: chocolate beverage alone (50g carbohydrate), or added with 24g oat, pea or rice proteins. Twenty Chinese males (mean±SD age 26±5years; body mass index 21.5±1.7kg/m2) ingested the test drink after an overnight fast. Venous blood samples and subjective appetite ratings were collected before test beverage and at fixed intervals for 180min. Blood biochemical data and appetite ratings were compared using repeated-measures ANOVA. Significant interaction effects were found in postprandial glucose excursions (time×protein effects, p=0.003). Glucose iAUC was lower in pea and rice proteins, although not significantly (p>0.385). Insulin iAUC was significantly higher in the oat (p=0.035) and pea (p=0.036) protein beverages. GIP and GLP-1 release in a sub-sample (n=10) followed a comparable order as insulin release (p=0.397 and 0.454, respectively). Significant interaction effects were found in fullness ratings (p=0.024), and a trend of greater suppression of hunger and desire-to-eat was also documented (p=0.088 and 0.080, respectively). Plant proteins altered the glycemic and appetitive responses of Asian males to a sugar-sweetened beverage. Food-based interventions are useful in promoting glycemic control. This trial was registered with ClinicalTrials.gov as NCT02933424.

An Overview on the Methods of Screening Antiobesity Activity

Purpose : The incidence of obesity around the world continues to increase and is considered a major cause of morbidity and mortality through various diseases. Various animal models can be used for the study of various compounds for the discovery of a novel treatment for the obesity. It can range from food intake studies in lean rodents to studies in obese animals due to high fat diet. The use of these animals helps us to determine whether the weight loss is due to fat loss or due to changes in other parameters. Various behavioral models can be used to study the food intake pattern and the effect of the drug on that pattern. These animal models have very good predictive validity as the effect of the drug on the animal models form the basis for the effect of the drug in humans. The drug induced weight loss in humans can be predicted to an extent from the studies carried out on these animal models. Approach : The published articles from Pubmed and other standard resources are used to study, review and compile the overview on screening methods used in Anti-obesity activity. Findings : The animal models of obesity can be used to study about the effects of parameters like insulin level, resistance and leptin levels in obesity. Acute and chronic feeding studies can be carried out. While studying about anti-obesity drugs the factors that lead to weight gain has to be considered. Conclusion : The obesity can be genetic or may be due to some other reason. The common cause for obesity is food intake with high calories and fat. So diet induced obese animal models are an important part of the studies. The animal models for the drug induced weight gain helps in the study of the effect of antiobesity drugs on the drug induced weight gain. All these models have been found to have utility in predicting the weight loss in obesity in man.

Impact of bread making on fructan chain integrity and effect of fructan enriched breads on breath hydrogen, satiety, energy intake, PYY and ghrelin.

Recently, there has been considerable interest in the satiety inducing properties of inulin type fructans (ITF) as a tool for weight management. As a staple food, breads provide an excellent vehicle for ITF supplementation however the integrity of the ITF chains and properties upon bread making need to be assessed. Breads enriched with 12% fructooligosaccharides (FOS) and 12% inulin were baked and the degree of polymerisation of fructans extracted from the breads were compared to those of pure compounds. An acute feeding study with a single blind cross-over design was conducted with 11 participants to investigate the effect of ITF enriched breads on breath hydrogen, self-reported satiety levels, active ghrelin, total PYY and energy intake. Size exclusion chromatography indicated that little or no depolymerisation of inulin occurred during bread making, however, there was evidence of modest FOS depolymerisation. Additionally, ITF enriched breads resulted in increased concentrations of exhaled hydrogen although statistical significance was reached only for the inulin enriched bread (p = 0.001). There were no significant differences between bread types in reported satiety (p = 0.129), plasma active ghrelin (p = 0.684), plasma PYY (p = 0.793) and energy intake (p = 0.240). These preliminary results indicate that inulin enriched bread may be a suitable staple food to increase ITF intake. Longer intervention trials are required to assess the impact of inulin enriched breads on energy intake and body weight.

Protein requirements and aging 1

Protein requirements and aging 1

Genetic and phenotypic determinants of flavonoid absorption and metabolism: the COB study

Background Flavonoids are present in numerous plant foods, including fruits, vegetables, teas, red wine, cocoa, herbs, and spices. Epidemiological data, along with evidence from cell, animal, and limited human intervention trial studies suggest that flavonoids can improve cardiovascular health and reduce the risk of other ageing-related diseases [1-6]. However, the absorption and metabolism of flavonoids, their metabolite profile, and their associated health benefits are highly heterogeneous [7], with the aetiological basis of this variability currently unknown. Our recent stable isotope study, which fed an oral bolus dose of 500 mg 13 C-labeled cyanidin-3-glucoside to healthy men showed a wide inter-individual variability in anthocyanin metabolism [7]. Methods The COB (Chocolate, Orange and Blackberry) study is examining the influence of genotype, age, gender and composition of the intestinal microbiota on the absorption, metabolism and elimination (AME) of flavonoids. It is an acute feeding study with mixed-flavonoids (containing flavan-3-ols, flavanones and anthocyanins) conducted in 120 men and 120 women (Caucasians, of European Origin), from two different age groups, 18-30 y and 65-77 y. The parent flavonoids and their metabolites will be measured in plasma and urine for up to 48 hours post-feeding. Participants’ genotypes will be established using exome sequencing and targeted genotyping for Single Nucleotide Popymorphisms (SNPs) in genes associated with i) pathways involved in flavonoid metabolism (in particular phase 1 and 2 enzymes); ii) genes that may alter the intestinal microbial composition; and iii) those modulating gut physiology. The composition of the gut microflora will be analysed by pyrosequencing of 16S rRNA and metagenomic technologies. Results

Meal skipping and variables related to energy balance in adults: A brief review, with emphasis on the breakfast meal

A popular notion regarding habitual meal skipping is that it leads to weight gain; however, there is little support for this idea in the scientific literature. Here we review the evidence both for and against this notion in adults (≥18years), with, out of practicality, a primary focus on the breakfast meal. To date, few randomized controlled trials and prospective studies have been conducted on breakfast skipping and energy balance. Three acute feeding studies have been published which show equivocal results and do not strongly support an effect of breakfast skipping on variables related to energy balance. Four longer-term experimental studies lasting 2–3weeks have been published and are consistent with the acute feeding trials in that breakfast skipping or eating treatments did not materially impact weight change. Four prospective studies in which participants were followed-up for over 3.7–10years do suggest a potential role of skipping breakfast in weight gain. However, observational studies do not imply causality; therefore, longer term experimental trials are needed before a definitive conclusion can be made concerning the role of breakfast skipping in weight change.

Influence of the tolerability of vinegar as an oral source of short-chain fatty acids on appetite control and food intake

Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice, and it is unclear if poor product palatability may explain previously published effects on appetite. To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two sequential and related acute human feeding studies. Healthy, young, normal weight unrestrained eaters were recruited to Study 1 (n=16), an acute feeding study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar control; and to Study 2 (n=14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar control following a milkshake preload. Both studies were a randomized crossover balanced design for the assessment of appetite, energy intake and glycaemic response. In Study 1, ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were accompanied by significantly higher nausea ratings, with unpalatable treatment having the greatest effect. Significant correlations between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence subsequent subjective or quantitative measures of appetite compared with control. These studies indicate that vinegar ingestion enhances satiety whereas orosensory stimulation alone does not, and that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of vinegar as a natural appetite suppressant does not seem appropriate.

Fish oil increases blood flow in the ileum during chronic feeding in rats

Benefits of enteral feeding with immune-enhancing diets (IEDs) depend on route, timing, and composition. We hypothesized that chronic enteral feeding with certain individual immunonutrients would enhance gastrointestinal blood flow. Male rats were fed a standard enteral diet supplemented with immunonutrients for 5 days before study. Groups were (1) standard rat chow, (2) liquid control diet (CD) alone (CD), (3) CD + fish oil, (4) CD + l-arginine, and (5) CD + RNA fragments. Whole organ blood flow distribution was measured by colorimetric microsphere technique in antrum, small intestine (in thirds), colon, liver, spleen, pancreas, and kidneys. Chronic feeding for 5 days with CD + fish oil increased blood flow in the distal third of the small intestine compared with CD alone, whereas feeding with CD + l-arginine decreased blood flow in the small intestine (all segments) compared with CD alone. Acute gavage of CD + l-arginine or CD + fish oil increased blood flow in the proximal and middle third of the small intestine compared with CD alone. Control diet + RNA increased blood flow in the proximal small intestine compared with CD alone. These findings support prior acute feeding studies with CD, CD + individual immunonutrients, or IED. Our current data suggest that blood flow benefits associated with fish oil persist during chronic feeding in rats. Enhanced gastrointestinal perfusion might partially explain the benefits of early enteral feeding with IEDs not seen with regular enteral diets and parenteral immunonutrient delivery.

Identification and in Vivo and in Vitro Characterization of Long Acting and Melanocortin 4 Receptor (MC4-R) Selective α-Melanocyte-Stimulating Hormone (α-MSH) Analogues

We report in vitro and in vivo data of new α-melanocyte-stimulating hormone (α-MSH) analogues which are N-terminal modified with a long chain fatty acid derivative. While keeping the pharmacophoric motif (d-Phe-Arg-Trp) fixed, we tried to improve selectivity and physicochemical parameters like solubility and stability of these analogues by replacing amino acids further away from the motif. Receptor specific changes in binding affinity to the melanocortin receptors were observed between the acetyl derivatives and the fatty acid analogues. Furthermore, amino acids at the N-terminal of α-MSH (Ser-Tyr-Ser) not considered to be part of the pharmacophore were found to have an influence on the MC4/MC1 receptor selectivity. While the acetyl analogues have an in vivo effect for around 7 h, the long chain fatty acid analogues have an effect up to 48 h in an acute feeding study in male Sprague-Dawley rats after a single subcutaneous administration.

Effects of a novel propionate-rich sourdough bread on appetite and food intake

There is evidence linking oral propionate to a reduction in food intake, which could confer functional food properties in the fight against obesity. However, propionate is typically volatile with a pungent smell and taste and so incorporating into foods naturally, at levels acceptable to the consumer is a novel approach. Twenty healthy, young, normal weight unrestrained eaters underwent an acute feeding study using a palatable sourdough and an identical control bread of a similar palatability, in a randomized cross-over balanced design for the assessment of appetite and energy intake. No difference in energy intake of an ad libitum test meal, 180 min after the bread-based breakfast or in energy and macronutrient intake over the entire 24 h period was found between breads. Visual analogue scale ratings for appetite were not influenced by bread type, except the desire to eat something sweet. Elevated plasma insulin concentrations were observed following the propionate-rich sourdough breakfast (P=0.033 no effects of treatment on postprandial glycaemia were found. These findings suggest propionate-rich sourdough bread does not influence appetite and food intake unlike larger doses of the food preservative N-propionate.

Serendipitous discovery of a new class of agonists for the melanocortin 1 and 4 receptors and a new class of cyclophanes

A new class of melanocortin 4 receptor (MC4r) agonists was discovered from an unexpected sidereaction in which formaldehyde caused cyclization. These cyclophanes were found to be sub micromolar agonists of the MC1 and MC4 and were less potent on the MC3 and MC5 receptor. They were shown to compete with the peptidic antagonist SHU9119 for binding to the MC4 receptor. In an acute feeding study in Sprague Dawley rats, food intake was reduced more than 50% versus vehicle after 3 h at a dose of 1 mg/kg.