Audrey E. Brynes

Gut hormone PYY3-36 physiologically inhibits food intake

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

Human gene for physical performance

A specific genetic factor that strongly influences human physical performance has not so far been reported, but here we show that a polymorphism in the gene encoding angiotensin-converting enzyme does just that. An ‘insertion’ allele of the gene is associated with elite endurance performance among high-altitude mountaineers. Also, after physical training, repetitive weight-lifting is improved eleven-fold in individuals homozygous for the ‘insertion’ allele compared with those homozygous for the ‘deletion’ allele.

Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.

BACKGROUND The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training. We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS We used three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical training. FINDINGS Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION II genotype, as a marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors.

The effects of fiber enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal

Objective: To assess whether the addition of viscous fiber at an amount recommended by the US FDA to allow a ‘low saturated fat, cholesterol, soluble fiber and coronary heart disease’, health claim label on a food package (1.7 g psyllium) and/or fat (30 g sunflower oil and 3 g sodium propionate) to a pasta meal would affect gastric emptying, postprandial glucose, insulin and GLP-1 concentrations.Design: Ten subjects participated in a two-by-two single blind randomized crossover study. Four meals containing 50 g of available carbohydrate were consumed: pasta with or without psyllium enrichment served with a tomato sauce with (520 kcal per meal) and without (240 kcal per meal) fat. Blood samples were taken for 240 min following the meal and all subjects consumed a buffet meal at the end of the study. Gastric empting was measured using the paracetamol absorption test. Blood was analysed for glucose, insulin, GLP-1. Visual analog scales were used to record feelings of hunger, pleasantness and nausea.Results: The psyllium-enriched pasta had no significant effect on gastric emptying or the incremental area under the curve (IAUC) for GLP-1, insulin or glucose compared with the control pasta. The addition of polyunsaturated fat and sodium propionate significantly increased the IAUC for GLP-1 (P<0.001), delaying gastric emptying (P<0.002), and decreasing glucose (P<0.002).Conclusions: A dose of 1.7 g psyllium did not evoke measurable effects on gastric emptying, postprandial GLP-1, insulin or glucose metabolism. However the addition of 30 g of oil and 3 g of sodium propionate to the pasta did reduce gastric emptying, increase GLP-1 and reduce glucose and insulin concentrations. While this short-term study may have implications in terms of reducing the risk of diabetes and improving coronary risk factor profiles the long term effects of these nutrients need to be studied.Sponsorship: This study was supported by Kellogg Company.

Preferential loss of visceral fat following aerobic exercise, measured by magnetic resonance imaging.

The aim of this study was to use whole-body magnetic resonance imaging (MRI) together with biochemical and anthropometric measurements to study the influence of regular moderate exercise with no dietary intervention on adipose tissue distribution in nonobese healthy women. We found significant decreases in both total (28.86±2.24 vs. 27.00±2.27 liters, P<0.05) and regional fat depots (visceral fat: 1.68±0.21 vs. 1.26±0.18 liters, P<0.01) using whole-body MRI despite no significant change in body weight, body mass index, or the waist-to-hip ratio. Interestingly, no changes in body fat content were found using anthropometry or impedance. There was a significant increase in high density lipoprotein cholesterol (1.58 ±0.06 vs. 1.66±0.08 mmol/L P<0.02) following exercise although there were no changes in other blood lipids such as triglycerides. In summary, moderate aerobic exercise over a period of 6 mon resulted in a preferential loss in visceral fat in nonobese healthy women, and this may help to explain some of the health benefits associated with regular and moderate physical activity.

Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study

IntroductionThe nutritional status of patients in the intensive care unit (ICU) appears to decline not only during their stay in the ICU but also after discharge from the ICU. Recent evidence suggests that gut released peptides, such as ghrelin and peptide YY (PYY) regulate the initiation and termination of meals and could play a role in the altered eating behaviour of sick patients. The aim of this study was to assess the patterns of ghrelin and PYY levels during the stay of ICU patients in hospital.MethodsSixteen ICU patients (60 ± 4.7 years, body mass index (BMI) 28.1 ± 1.7 kg/m2 (mean ± standard error of the mean)) underwent fasting blood sample collections on days 1, 3, 5, 14, 21 and 28 of their stay at Hammersmith and Charing Cross Hospitals. Changes in appetite and biochemical and anthropometric markers of nutritional status were recorded. A comparison was made to a group of 36 healthy volunteers matched for age and BMI (54.3 ± 2.9 years, p = 0.3; BMI 25.8 ± 0.8 kg/m2p = 0.2).ResultsCompared to healthy subjects, ICU patients exhibited a significantly lower level of ghrelin (day one 297.8 ± 76.3 versus 827.2 ± 78.7 pmol/l, p < 0.001) during their stay in the ICU. This tended to rise to the normal level during the last three weeks of hospital stay. Conversely, ICU patients showed a significantly higher level of PYY (day one 31.5 ± 9.6 versus 11.3 ± 1.0 pmol/l, p < 0.05) throughout their stay in the ICU and on the ward, with a downward trend to the normal level during the last three weeks of stay.ConclusionsResults from our study show high levels of PYY and low levels of ghrelin in ICU patients compared to healthy controls. There appears to be a relationship between the level of these gut hormones and nutritional intake.

A prospective randomised trial to determine the efficacy of a low glycaemic index diet given in addition to healthy eating and weight loss advice in patients with coronary heart disease.

Objective: Recent epidemiological and prospective trial evidence suggests that consumption of a low glycaemic index (LGI) diet will reduce coronary risk. We hypothesise that introduction of an LGI diet will improve the metabolic profile of patients who have undergone coronary artery bypass grafting.Design: We conducted a randomised parallel group trial comparing a control group (n=29, age 61.8±9 y), who received currently advocated healthy eating dietary advice only, to an intervention group, who received healthy eating advice emphasising LGI carbohydrates (n=26, age 63.6±9.4 y) over a 12-week period in free-living patients with coronary heart disease. Outcome measures included fasting glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides.Results: A significant lower dietary glycaemic index was achieved in the group assigned to an LGI diet compared to the healthy eating control group (71±1 vs 81±1); fibre intake was also higher in the LGI group (20±1 vs 15±1 g). All biochemical markers of glucose and lipid metabolism measured were similar after 12 weeks of the LGI diet or control diet.Discussion: The LGI group achieved a significant LGI and a higher dietary fibre intake. However, there was no measurable significant effect of either the LGI diet or the health eating diet on lipid levels; this may have been hidden by concurrent drug therapy.

Proglucagon-Derived Peptides in Intestinal Epithelial Proliferation

Proglucagon-derived peptides have been implicated in the control of intestinal mucosal cell division. To investigate the actions of these peptides on intestinal cell proliferation, different doses of enteroglucagon, oxyntomodulin, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were tested in male Wistar rats maintained on total parenteral nutrition. Crypt cell proliferation was assessed by the analysis of arrested metaphases in microdissected crypts. Enteroglucagon and oxyntomodulin had no effect on intestinal weight or cell proliferation. GLP-1 had a slight effect on stomach and small intestinal weights and on epithelial cell proliferation in the small and large intestines. GLP-2 infusion dose-dependently increased the weights of the stomach, small intestine, colon, and cecum and increased crypt cell proliferation in the small and large intestines of parenterally fed rats. In orally fed animals, GLP-2 increased intestinal weight but had little effect on proliferation. Therefore, of the proglucagon-derived peptides, GLP-2 appears to be a major mediator of intestinal epithelial proliferation.

The beneficial effect of a diet with low glycaemic index on 24 h glucose profiles in healthy young people as assessed by continuous glucose monitoring.

Elevated postprandial glycaemia has been linked to CVD in a number of different epidemiological studies involving predominantly non-diabetic volunteers. The MiniMed continuous glucose monitor, which measures blood glucose every 5 min, over a 24 h period, was used to investigate changes in blood glucose readings before and after instigating a diet with low glycaemic index (GI) for 1 week in free-living healthy individuals. Nine healthy people (age 27 (SEM 1.3) years, BMI 23.7 (SEM 0.7) kg/m2, one male, eight females) completed the study. A reduction in GI (59.7 (SEM 2) v. 52.1 (SEM 2), P<0.01) occurred in all nine subjects while energy and other macronutrients remained constant. A significant reduction was also observed in fasting glucose at 06.00 hours (5.4 (SEM 0.2) v. 4.4 (SEM 0.3) mmol/l, P<0.001), mean glucose (5.6 (SEM 0.2) v. 5.1 (SEM 0.2) mmol/l, P=0.004), area under the 24 h glucose curve (8102 (SEM 243) v. 750 (SEM 235) mmol/l per min, P=0.004) and area under the overnight, 8 h glucose curve (2677 (SEM 92) v. 2223 (SEM 121) mmol/l per min, P=0.01). The present study provides important data on how a simple adjustment to the diet can improve glucose profiles that, if sustained in the long term, would be predicted from epidemiological studies to have a favourable influence on CVD.

Gastrointestinal responses to a panel of lectins in rats maintained on total parenteral nutrition.

Total parenteral nutrition (TPN) causes atrophy of gastrointestinal epithelia, so we asked whether lectins that stimulate epithelial proliferation can reverse this effect of TPN. Two lectins stimulate pancreatic proliferation by releasing CCK, so we asked whether lectins that stimulate gastrointestinal proliferation also release hormones that might mediate their effects. Six rats per group received continuous infusion of TPN and a once daily bolus dose of purified lectin (25 mg ⋅ rat-1 ⋅ day-1) or vehicle alone (control group) for 4 days via an intragastric cannula. Proliferation rates were estimated by metaphase arrest, and hormones were measured by RIAs. Phytohemagglutinin (PHA) increased proliferation by 90% in the gastric fundus ( P < 0.05), doubled proliferation in the small intestine ( P < 0.001), and had a small effect in the midcolon ( P< 0.05). Peanut agglutinin (PNA) had a minor trophic effect in the proximal small intestine ( P < 0.05) and increased proliferation by 166% in the proximal colon ( P < 0.001) and by 40% in the midcolon ( P < 0.001). PNA elevated circulating gastrin and CCK by 97 ( P< 0.05) and 81% ( P < 0.01), respectively, and PHA elevated plasma enteroglucagon by 69% and CCK by 60% (both P < 0.05). Only wheat germ agglutinin increased the release of glucagon-like peptide-1 by 100% ( P < 0.05). PHA and PNA consistently reverse the fall in gastrointestinal and pancreatic growth associated with TPN in rats. Both lectins stimulated the release of specific hormones that may have been responsible for the trophic effects. It is suggested that lectins could be used to prevent gastrointestinal atrophy during TPN. Their hormone-releasing effects might be involved.