Publications
69 results found
Chambers E, Byrne C, Morrison D, et al., 2019, Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial, Gut, Vol: 68, Pages: 1430-1438, ISSN: 0017-5749
Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.Design: Twelve non-diabetic adults with overweight and obesity received 20g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo controlled, crossover design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.Results: Both IPE and inulin supplementation improved insulin resistance compared to cellulose supplementation, measured by homeostatic model assessment (HOMA) 2 (Mean±SEM 1.23±0.17 IPE vs. 1.59±0.17 cellulose, P=0.001; 1.17±0.15 inulin vs. 1.59±0.17 cellulose, P=0.009), with no differences between IPE and inulin (P=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased pro-inflammatory IL-8 levels compared to cellulose, whilst inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridales) compared to cellulose, with small differences at the species level observed between IPE and cellulose. Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.
Lloyd AJ, Willis ND, Wilson T, et al., 2019, Developing a food exposure and urine sampling strategy for dietary exposure biomarker validation in free-living individuals, Molecular Nutrition and Food Research, Vol: 63, Pages: 1-9, ISSN: 1613-4125
SCOPE: Dietary choices modulate the risk of chronic diseases and improving diet is a central component of public health strategies. Food-derived metabolites present in urine could provide objective biomarkers of dietary exposure. To assist biomarker validation we aimed to develop a food intervention strategy mimicking a typical annual diet over a short period of time and assessed urine sampling protocols potentially suitable for future deployment of biomarker technology in free-living populations. METHODS AND RESULTS: Six different menu plans representing comprehensively a typical UK annual diet that were split into two dietary experimental periods. Free-living adult participants (n = 15 and n = 36, respectively) were provided with all their food, as a series of menu plans, over a period of 3 consecutive days. Multiple spot urine samples were collected and stored at home. CONCLUSION: We established a successful food exposure strategy following a conventional UK eating pattern, which was suitable for biomarker validation in free-living individuals. The urine sampling procedure was acceptable for volunteers and delivered samples suitable for biomarker quantification. Our study design provides scope for validation of existing biomarker candidates and potentially for discovery of new biomarker-leads and should help inform the future deployment of biomarker technology for habitual dietary exposure measurement.
Chambers E, 2019, Gut-derived short chain fatty acids: A friend or foe for hepatic lipid metabolism?, Nutrition Bulletin, Vol: 44, Pages: 154-159, ISSN: 1467-3010
This article describes how a British Nutrition Foundation Drummond Pump Priming Award was used to develop in vivo proof of concept for increasing colonic propionate as a therapeutic strategy to reduce liver fat in adults with non‐alcoholic fatty disease (NAFLD). An overview of how the gut‐derived short‐chain fatty acids propionate and acetate are taken up and metabolised by the liver is provided, as well as a summary of how acetate may have contrasting effects on hepatic lipid content depending on the metabolic health of the individual. Finally, the article proposes that raising colonic propionate production could interfere with hepatic acetate metabolism and have positive effects on liver fat accumulation in individuals with NAFLD.
Lloyd AJ, Willis ND, Wilson T, et al., 2019, Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake, Metabolomics, Vol: 15, ISSN: 1573-3882
IntroductionDietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment.ObjectivesTo test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body.MethodsWe designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36).ResultsThe experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables.ConclusionIt was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies.
Byrne C, Chambers E, Brignardello J, et al., 2019, Effects of inulin propionate ester incorporated into palatable food products on appetite and resting energy expenditure: a randomised crossover study, Nutrients, Vol: 11, ISSN: 2072-6643
Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.
Byrne C, Blunt D, Burn J, et al., 2019, A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans, F1000Research, Vol: 8, ISSN: 2046-1402
Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. Registratio
Chambers ES, Byrne CS, Frost G, 2019, Carbohydrate and human health: is it all about quality?, LANCET, Vol: 393, Pages: 384-386, ISSN: 0140-6736
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Chambers ES, Preston T, Frost G, et al., 2018, Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health., Curr Nutr Rep, Vol: 7, Pages: 198-206
PURPOSE OF THIS REVIEW: This review assesses the latest evidence linking short-chain fatty acids (SCFA) with host metabolic health and cardiovascular disease (CVD) risk and presents the latest evidence on possible biological mechanisms. RECENT FINDINGS: SCFA have a range of effects locally in the gut and at both splanchnic and peripheral tissues which together appear to induce improved metabolic regulation and have direct and indirect effects on markers of CVD risk. SCFA produced primarily from the microbial fermentation of dietary fibre appear to be key mediators of the beneficial effects elicited by the gut microbiome. Not only does dietary fibre fermentation regulate microbial activity in the gut, SCFA also directly modulate host health through a range of tissue-specific mechanisms related to gut barrier function, glucose homeostasis, immunomodulation, appetite regulation and obesity. With the increasing burden of obesity worldwide, the role for gut microbiota-generated SCFA in protecting against the effects of energy dense diets offers an intriguing new avenue for regulating metabolic health and CVD risk.
Ezekwe SI, Gibson R, Frost G, et al., 2018, A comparison of glycaemic variability in healthy shift workers during night and day shift work using mean amplitude of glycaemic excursions (MAGE), Publisher: WILEY, Pages: 80-80, ISSN: 0742-3071
Chambers E, Frost G, Byrne C, et al., 2017, Acute oral sodium propionate supplementation raises resting energy expenditure and lipid oxidation in fasted humans, Diabetes, Obesity and Metabolism, Vol: 20, Pages: 1034-1039, ISSN: 1462-8902
Short‐chain fatty acids (SCFAs), produced from fermentation of dietary fibre by the gut microbiota, have been suggested to modulate energy metabolism. Previous work using rodent models has demonstrated that oral supplementation of the SCFA propionate raises resting energy expenditure (REE) by promoting lipid oxidation. The objective of the present study was to investigate the effects of oral sodium propionate on REE and substrate metabolism in humans. Eighteen healthy volunteers (9 women and 9 men; age 25 ± 1 years; body mass index 24.1 ± 1.2 kg/m2) completed 2 study visits following an overnight fast. Tablets containing a total of 6845 mg sodium propionate or 4164 mg sodium chloride were provided over the 180‐minute study period in random order. REE and substrate oxidation were assessed by indirect calorimetry. Oral sodium propionate administration increased REE (0.045 ± 0.020 kcal/min; P = .036); this was accompanied by elevated rates of whole‐body lipid oxidation (0.012 ± 0.006 g/min; P = .048) and was independent of changes in glucose and insulin concentrations. Future studies are warranted to determine whether the acute effects of oral sodium propionate on REE translate into positive improvements in long‐term energy balance in humans.
Garcia Perez I, Posma JM, Gibson R, et al., 2017, Modernizing dietary assessment, IUNS 21st ICN International Congress of Nutrition, Publisher: Karger Publishers, Pages: 286-287, ISSN: 1421-9697
Garcia Perez I, Posma JM, Gibson R, et al., 2017, Objective assessment of dietary patterns using metabolic phenotyping: a randomized, controlled, crossover trial, The Lancet Diabetes & Endocrinology, Vol: 5, Pages: 184-195, ISSN: 2213-8587
Background: The burden of non-communicable diseases, such as obesity, diabetes, coronary heart disease and cancer, can be reduced by the consumption of healthy diets. Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, many of them influenced by food intake. We aim to classify people according to dietary behaviour and enhance dietary reporting using metabolic profiling of urine.Methods: To develop metabolite models from 19 healthy volunteers who attended a clinical research unit for four day periods on four occasions. We used the World Health Organisation’s healthy eating guidelines (increase fruits, vegetables, wholegrains, dietary fibre and decrease fats, sugars, and salt) to develop four dietary interventions lasting for four days each that ranged from a diet associated with a low to high risk of developing non-communicable disease. Urine samples were measured by 1H-NMR spectroscopy. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN 43087333. INTERMAP U.K. (n=225) and a healthy-eating Danish cohort (n=66) were used as free-living validation datasets.Findings: There was clear separation between the urinary metabolite profiles of the four diets. We also demonstrated significant stepwise differences in metabolite levels between the lowest and highest metabolic risk diets and developed metabolite models for each diet. Application of the derived metabolite models to independent cohorts confirmed the association between urinary metabolic and dietary profiles in INTERMAP (P<0•001) and the Danish cohort (P<0•001).Interpretation: Urinary metabolite models, developed in a highly controlled environment, can classify groups of free-living people into consumers of dietary profiles associated with lower or higher non-communicable disease risk based on multivariate m
Lloyd AJ, Zubair H, Willis ND, et al., 2016, Quantification of dietary biomarkers in spot urine samples reflects the intake of foods of UK high public health importance, Publisher: Cambridge University Press (CUP), Pages: E248-E248, ISSN: 0029-6651
An understanding of causal relations between diet and health is hindered by the lack of robust biological markers of food exposure (1).The rapid development of metabolomics technology offers opportunity for the identification of urine biomarkers for the intake of arange of foods of high public health importance (2), (3). Using high mass resolution mass spectrometry and machine learning data analysis,we have discovered potential urinary biomarkers in controlled clinical studies with a range of analytical techniques (2). To haveutility for population monitoring, we aim to validate biomarker performance in free-living individuals using urine samples collected inthe home with a minimal impact on normal daily activities.Two complementary multiple reaction monitoring (MRM) routines using triple quadrupole mass spectrometry (QQQ-MS) havebeen developed to quantify concurrently dietary exposure biomarkers of more than 20 foods of high public health importance inthe UK. MRM quantification of metabolite levels in spot urines collected either before bed time or a first morning void identifieda sub-set of potential biomarkers that demonstrated robust linkage with reported dietary intake (examples in Table 1). Figure 1demonstrates the ability of selected biomarkers to report exposure in relation to muscle meat intake from lunch time to bedtime(Beefburger; 106gm, Chicken breast; 130gm; Processed Ham; 40·5 gm) in 6 free-living individuals. Anserine was strongly, and specifically,associated with poultry intake, whilst the urinary outputs of 3-methyl histidine and carnosine reflect striated muscle intake,with levels substantially reduced when meals contain lower quality, and processed, meats with reduced levels of striated musclecontent.
Petropoulou K, Chambers ES, Morrison DJ, et al., 2016, Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis, Nutrition Bulletin, Vol: 41, Pages: 372-377, ISSN: 1467-3010
Identifying dietary tools that prevent disordered insulin secretion from pancreatic β-cells is an attractive strategy to combat the increasing prevalence of type 2 diabetes. Dietary resistant starch has been linked to improvements in the function of β-cells, possibly via increased colonic fermentation and production of short-chain fatty acids (SCFAs). Increasing the resistant starch content of commonly consumed foods could therefore maintain glucose homeostasis at the population level. As part of Biotechnology and Biological Sciences Research Council (BBSRC) Diet and Health Research Industry Club (DRINC) initiative, variants of Pisum sativum L. (pea) are being investigated to identify the features of pea starch that make it resistant to digestion and available for colonic fermentation and SCFA production. Parallel in vitro and in vivo studies are being conducted using both whole pea seeds and pea flour to facilitate a better understanding of how cells in the pea cotyledons are affected by processing and, in turn, how this influences starch digestibility. Trials in human volunteers are being used to monitor a full spectrum of short- and long-term physiological responses relevant to pancreatic β-cell function and glucose homeostasis. This project is providing new insights into variants of crops that are associated with the specific types of resistant starch that provide the best protection against defects in insulin secretion and function.
Pingitore A, Chambers ES, Hill T, et al., 2016, The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro, DIABETES OBESITY & METABOLISM, Vol: 19, Pages: 257-265, ISSN: 1462-8902
Polyviou T, MacDougall K, Chambers ES, et al., 2016, Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon., Alimentary Pharmacology and Therapeutics, Vol: 44, Pages: 662-672, ISSN: 0269-2813
BACKGROUND: Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans. AIMS: To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. METHODS: Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0-61 wt% (IPE-0-IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using (13) C-labelled IPE variants. RESULTS: In vitro, IPE-27-IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE-27 led to greater (13) C recovery in breath CO2 than IPE-54 (64.9 vs. 24.9%, P = 0.001). IPE-27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control. CONCLUSIONS: IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet-gut microbiome-host metabolism axis in humans.
Bottin JH, Swann JR, Cropp E, et al., 2016, Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial, British Journal of Nutrition, Vol: 116, Pages: 360-374, ISSN: 1475-2662
Dietary mycoprotein decreases energy intake in lean individuals. The effects in overweight individuals are unclear, and the mechanisms remain to be elucidated. This study aimed to investigate the effect of mycoprotein on energy intake, appetite regulation, and the metabolic phenotype in overweight and obese volunteers. In two randomised-controlled trials, fifty-five volunteers (age: 31 (95 % CI 27, 35) years), BMI: 28·0 (95 % CI 27·3, 28·7) kg/m2) consumed a test meal containing low (44 g), medium (88 g) or high (132 g) mycoprotein or isoenergetic chicken meals. Visual analogue scales and blood samples were collected to measure appetite, glucose, insulin, peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Ad libitum energy intake was assessed after 3 h in part A (n 36). Gastric emptying by the paracetamol method, resting energy expenditure and substrate oxidation were recorded in part B (n 14). Metabonomics was used to compare plasma and urine samples in response to the test meals. Mycoprotein reduced energy intake by 10 % (280 kJ (67 kcal)) compared with chicken at the high content (P=0·009). All mycoprotein meals reduced insulin concentrations compared with chicken (incremental AUClow (IAUClow): -8 %, IAUCmedium: -12 %, IAUChigh: -21 %, P=0·004). There was no significant difference in glucose, PYY, GLP-1, gastric emptying rate and energy expenditure. Following chicken intake, paracetamol-glucuronide was positively associated with fullness. After mycoprotein, creatinine and the deamination product of isoleucine, α-keto-β-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, β-hydroxybutyrate, was positively associated. In conclusion, mycoprotein reduces energy intake and insulin release in overweight volunteers. The mechanism does not involve changes in PYY and GLP-1. The metabonomics analysis may bring new understanding to the appetite regulatory properties of food.
Byrne CS, Chambers ES, Alhabeeb H, et al., 2016, Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods, American Journal of Clinical Nutrition, Vol: 104, ISSN: 1938-3207
BACKGROUND: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. OBJECTIVES: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. DESIGN: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). RESULTS: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. CONCLUSION: Our results suggest that colonic propionate production may play
Robinson SL, Chambers ES, Fletcher G, et al., 2016, Lipolytic Markers, Insulin and Resting Fat Oxidation are Associated with Maximal Fat Oxidation, International Journal of Sports Medicine, Vol: 37, Pages: 607-613, ISSN: 1439-3964
Garcia-Perez I, Posma JM, Chambers ES, et al., 2016, An analytical pipeline for quantitative characterization of dietary intake: application to assess grape intake., Journal of Agricultural and Food Chemistry, Vol: 64, Pages: 2423-2431, ISSN: 1520-5118
Lack of accurate dietary assessment in free-living populations requires discovery of new biomarkers reflecting food intake qualitatively and quantitatively to objectively evaluate effects of diet on health. We provide a proof-of-principle for an analytical pipeline to identify quantitative dietary biomarkers. Tartaric acid was identified as dose-responsive urinary biomarker of grape intake and subsequently quantified in volunteers who followed a series of 4-day dietary interventions incorporating 0g/day, 50g/day, 100g/day and 150g/day of grapes in standardized diets from a randomized controlled clinical trial. The most accurate quantitative prediction of grape intake was obtained in 24h urine samples which have the strongest linear relationship between grape intake and tartaric acid excretion (r2=0.90). This new methodological pipeline for estimating nutritional intake based on coupling dietary intake information and quantified nutritional biomarkers was developed and validated in a controlled dietary intervention study, showing that this approach can improve the accuracy of estimating nutritional intakes.
Salem V, Izzi-Engbeaya C, Coello C, et al., 2016, Glucagon increases energy expenditure independently of brown adipose tissue activation in humans, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 18, Pages: 72-81, ISSN: 1462-8902
Aims: To investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans.Methods: Indirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent ¹⁸F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on ¹⁸F-FDG PET/CT (n = 8) underwent a randomly allocated second ¹⁸F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4).Results: We observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on ¹⁸F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not.Conclusions: Glucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE.
Chambers ES, Viardot A, Psichas A, et al., 2015, Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults, Gut, Vol: 64, Pages: 1744-1754, ISSN: 0017-5749
Objective The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.Design To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.Results Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.
Byrne CS, Chambers ES, Morrison DJ, et al., 2015, The role of short chain fatty acids in appetite regulation and energy homeostasis, International Journal of Obesity, Vol: 39, Pages: 1331-1338, ISSN: 1476-5497
Over the last 20 years there has been an increasing interest in the influence of the gastrointestinal tract on appetite regulation.Much of the focus has been on the neuronal and hormonal relationship between the gastrointestinal tract and the brain. There isnow mounting evidence that the colonic microbiota and their metabolic activity have a significant role in energy homeostasis. Thesupply of substrate to the colonic microbiota has a major impact on the microbial population and the metabolites they produce,particularly short chain fatty acids (SCFAs). SCFAs are produced when non-digestible carbohydrates, namely dietary fibres andresistant starch, undergo fermentation by the colonic microbiota. Both the consumption of fermentable carbohydrates and theadministration of SCFAs have been reported to result in a wide range of health benefits including improvements in bodycomposition, glucose homeostasis, blood lipid profiles and reduced body weight and colon cancer risk. However, published studiestend to report the effects that fermentable carbohydrates and SCFAs have on specific tissues and metabolic processes, and fail toexplain how these local effects translate into systemic effects and the mitigation of disease risk. Moreover, studies tend toinvestigate SCFAs collectively and neglect to report the effects associated with individual SCFAs. Here, we bring together the recentevidence and suggest an overarching model for the effects of SCFAs on one of their beneficial aspects: appetite regulation andenergy homeostasis.
Chambers ES, Morrison DJ, Tedford MC, et al., 2015, A novel dietary strategy to increase colonic propionate production in humans and improve appetite regulation and bodyweight management, NUTRITION BULLETIN, Vol: 40, Pages: 227-230, ISSN: 1471-9827
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Chambers ES, Morrison DJ, Frost G, 2015, Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms?, PROCEEDINGS OF THE NUTRITION SOCIETY, Vol: 74, Pages: 328-336, ISSN: 0029-6651
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- Citations: 166
Robinson SL, Hattersley J, Frost GS, et al., 2015, Maximal fat oxidation during exercise is positively associated with 24-hour fat oxidation and insulin sensitivity in young, healthy men, JOURNAL OF APPLIED PHYSIOLOGY, Vol: 118, Pages: 1415-1422, ISSN: 8750-7587
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Chambers ES, Viardot A, Psichas A, et al., 2015, Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease: a pilot study, Proceedings of the Nutrition Society, Vol: 74, Pages: E30-E30, ISSN: 1475-2719
Sam AH, Sleeth ML, Thomas EL, et al., 2015, Circulating pancreatic polypeptide concentrations predict visceral and liver fat content, Journal of Clinical Endocrinology and Metabolism, Vol: 100, Pages: 1048-1052, ISSN: 0021-972X
Context and objective:No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat.Patients and Methods:Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy.Results:Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01).Conclusions:Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.
Willis ND, Dodds SE, Lloyd AJ, et al., 2015, Dietary compliance in a human intervention study investigating the impact of specific foods on urinary metabolites, PROCEEDINGS OF THE NUTRITION SOCIETY, Vol: 74, Pages: E127-E127, ISSN: 0029-6651
Cegla J, Troke RC, Jones B, et al., 2014, Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake, Diabetes, Vol: 63, Pages: 3711-3720, ISSN: 0012-1797
Obesity is a growing epidemic, and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side effects. Both glucagon and GLP-1 reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. We hypothesized that the combination of both peptides, administered at doses that are individually subanorectic, would reduce appetite, while GLP-1 would protect against the hyperglycemic effect of glucagon. In this double-blind crossover study, subanorectic doses of each peptide alone, both peptides in combination, or placebo was infused into 13 human volunteers for 120 min. An ad libitum meal was provided after 90 min, and calorie intake determined. Resting energy expenditure was measured by indirect calorimetry at baseline and during infusion. Glucagon or GLP-1, given individually at subanorectic doses, did not significantly reduce food intake. Coinfusion at the same doses led to a significant reduction in food intake of 13%. Furthermore, the addition of GLP-1 protected against glucagon-induced hyperglycemia, and an increase in energy expenditure of 53 kcal/day was seen on coinfusion. These observations support the concept of GLP-1 and glucagon dual agonism as a possible treatment for obesity and diabetes.
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