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1.
Nat Metab ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32694821

RESUMO

A key metabolic activity of the gut microbiota is the fermentation of non-digestible carbohydrate, which generates short-chain fatty acids (SCFAs) as the principal end products. SCFAs are absorbed from the gut lumen and modulate host metabolic responses at different organ sites. Evidence suggests that these organ sites include skeletal muscle, the largest organ in humans, which plays a pivotal role in whole-body energy metabolism. In this Review, we evaluate the evidence indicating that SCFAs mediate metabolic cross-talk between the gut microbiota and skeletal muscle. We discuss the effects of three primary SCFAs (acetate, propionate and butyrate) on lipid, carbohydrate and protein metabolism in skeletal muscle, and we consider the potential mechanisms involved. Furthermore, we highlight the emerging roles of these gut-derived metabolites in skeletal muscle function and exercise capacity, present limitations in current knowledge and provide suggestions for future work.

2.
Br J Nutr ; 123(12): 1321-1332, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32100651

RESUMO

Mycoprotein is a food high in both dietary fibre and non-animal-derived protein. Global mycoprotein consumption is increasing, although its effect on human health has not yet been systematically reviewed. This study aims to systematically review the effects of mycoprotein on glycaemic control and energy intake in humans. A literature search of randomised controlled trials was performed in PubMed, Embase, Web of Science, Google Scholar and hand search. A total of twenty-one studies were identified of which only five studies, totalling 122 participants, met the inclusion criteria. All five studies were acute studies of which one reported outcomes on glycaemia and insulinaemia, two reported on energy intake and two reported on all of these outcomes. Data were extracted, and risk-of-bias assessment was then conducted. The results did not show a clear effect of acute mycoprotein on blood glucose levels, but it showed a decrease in insulin levels. Acute mycoprotein intake also showed to decrease energy intake at an ad libitum meal and post-24 h in healthy lean, overweight and obese humans. In conclusion, the acute ingestion of mycoprotein reduces energy intake and insulinaemia, whereas its impact on glycaemia is currently unclear. However, evidence comes from a very limited number of heterogeneous studies. Further well-controlled studies are needed to elucidate the short- and long-term effects of mycoprotein intake on glycaemic control and energy intake, as well as the mechanisms underpinning these effects.

3.
Metabolism ; 104: 154043, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31790692

RESUMO

BACKGROUND: Our previous work has shown that oral supplementation with inulin propionate ester (IPE) reduces intra-abdominal fat and prevents weight gain and that oral propionate intake enhances resting fat oxidation. The effects of IPE combined with exercise training on energy substrate utilisation are unknown. The aim of this study was to investigate the impact of 4-weeks IPE supplementation, in combination with a moderate intensity exercise training programme, on whole body fat oxidation and on plasma GLP-1 and PYY. METHODS: Twenty overweight healthy women participated in randomised parallel study and underwent 4 weeks of supervised exercise training either with IPE (EX/IPE group) or Placebo (EX/Placebo group) supplementation. Before and after the intervention participants conducted an experimental trial, which involved collection of expired gas and blood samples in the fasted state and during 7 h of the postprandial state. RESULTS: Within groups, the EX/IPE group significantly enhanced the amount of fat (Pre, 24.1 ±â€¯1.2 g; Post, 35.9 ±â€¯4.0 g, P < 0.05) oxidised and reduced CHO (Pre, 77.8 ±â€¯6.0 g; Post, 57.8 ±â€¯7.7 g, P < 0.05) oxidised, reduced body weight (Pre, 77.3 ±â€¯4.2 kg; Post, 76.6 ±â€¯4.1 kg, P < 0.05) and body fat mass (Pre, 37.7 ±â€¯1.9%; Post, 36.9 ±â€¯1.9%, P < 0.05). In EX/Placebo group, changes in amount of fat (Pre, 36.8 ±â€¯3.9 g; Post, 37.0 ±â€¯4.0 g) and CHO (Pre, 62.7 ±â€¯6.5 g; Post, 61.5 ±â€¯7.4 g) oxidised, body weight (Pre, 84.2 ±â€¯4.3 kg; Post, 83.6 ±â€¯4.3 kg) and body fat mass (Pre, 40.1 ±â€¯1.9%; Post, 38.7 ±â€¯1.5%) were not significant (P > 0.05). Comparing between groups, changes in the amount of fat oxidised were significantly (P < 0.05) different and a trend for difference was observed for amount of CHO oxidised (P = 0.06) and RER (P = 0.06). The interventions had no impact on fasting or postprandial plasma concentrations of GLP-1 and PYY. CONCLUSION: Moderate intensity exercise training programmes when combined with daily oral IPE supplementation may help overweight women to achieve increase in fat oxidation. The study was registered at clinicaltrials.gov as NCT04016350.


Assuntos
Gorduras na Dieta/metabolismo , Exercício Físico , Hipoglicemiantes/uso terapêutico , Inulina/uso terapêutico , Sobrepeso/metabolismo , Sobrepeso/terapia , Propionatos/uso terapêutico , Adiposidade , Adulto , Apetite , Peso Corporal , Terapia Combinada , Suplementos Nutricionais , Feminino , Hormônios/metabolismo , Humanos , Pessoa de Meia-Idade , Oxirredução , Método Simples-Cego
4.
Food Funct ; 11(1): 617-627, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31859318

RESUMO

Refined starchy foods are usually rapidly digested, leading to poor glycaemic control, but not all starchy foods are the same. Complex carbohydrates like resistant starch (RS) have been shown to reduce the metabolic risk factors for chronic diseases such as hyperglycaemia and overweight. The aim of the project was to develop a semolina-based food made from a starch branching enzyme II (sbeIIa/b-AB) durum wheat mutant with a high RS content and to measure its glycaemic index using a double-blind randomised pilot study. We report here the amylose, RS and non-starch polysaccharide concentration of raw sbeIIa/b-AB and wild-type control (WT) semolina. We measured RS after cooking to identify a model food for in vivo testing. Retrograded sbeIIa/b-AB semolina showed a higher RS concentration than the WT control (RS = 4.87 ± 0.6 g per 100 g, 0.77 ± 0.34 g per 100 g starch DWB, respectively), so pudding was selected as the test food. Ten healthy participants consumed ∼50 g of total starch from WT and sbeIIa/b-AB pudding and a standard glucose drink. Capillary blood glucose concentrations were measured in the fasting and postprandial state (2 h): incremental area-under-the-curve (iAUC) and GI were calculated. We found no evidence of difference in GI between sbeIIa/b-AB pudding and the WT control, but the starch digestibility was significantly lower in sbeIIa/b-AB pudding compared to the WT control in vitro (C90 = 33.29% and 47.38%, respectively). Based on these results, novel sbeIIa/b-AB wheat foods will be used in future in vivo studies to test the effect of different RS concentrations and different food matrices on glycaemia.

5.
J Nutr ; 149(10): 1692-1700, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31240300

RESUMO

BACKGROUND: Measurement of multiple food intake exposure biomarkers in urine may offer an objective method for monitoring diet. The potential of spot and cumulative urine samples that have reduced burden on participants as replacements for 24-h urine collections has not been evaluated. OBJECTIVE: The aim of this study was to determine the utility of spot and cumulative urine samples for classifying the metabolic profiles of people according to dietary intake when compared with 24-h urine collections in a controlled dietary intervention study. METHODS: Nineteen healthy individuals (10 male, 9 female, aged 21-65 y, BMI 20-35 kg/m2) each consumed 4 distinctly different diets, each for 1 wk. Spot urine samples were collected ∼2 h post meals on 3 intervention days/wk. Cumulative urine samples were collected daily over 3 separate temporal periods. A 24-h urine collection was created by combining the 3 cumulative urine samples. Urine samples were analyzed with metabolite fingerprinting by both high-resolution flow infusion electrospray mass spectrometry (FIE-HRMS) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Concentrations of dietary intake biomarkers were measured with liquid chromatography triple quadrupole mass spectrometry and by integration of 1H-NMR data. RESULTS: Cross-validation modeling with 1H-NMR and FIE-HRMS data demonstrated the power of spot and cumulative urine samples in predicting dietary patterns in 24-h urine collections. Particularly, there was no significant loss of information when post-dinner (PD) spot or overnight cumulative samples were substituted for 24-h urine collections (classification accuracies of 0.891 and 0.938, respectively). Quantitative analysis of urine samples also demonstrated the relation between PD spot samples and 24-h urines for dietary exposure biomarkers. CONCLUSIONS: We conclude that PD spot urine samples are suitable replacements for 24-h urine collections. Alternatively, cumulative samples collected overnight predict similarly to 24-h urine samples and have a lower collection burden for participants.

6.
J Endocrinol ; 242(2): R1-R8, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31042668

RESUMO

Short-chain fatty acids (SCFAs) are metabolites produced from the fermentation of dietary fibre by the gut microbiota. High-fibre diets have been associated with lower weight gain and a number of reports have therefore investigated if these positive effects of a dietary fibre on body weight can be replicated through the direct administration of SCFAs. Many of these studies have reported that SCFAs can prevent or attenuate long-term body weight gain by increasing energy expenditure through increased lipid oxidation. The aim of the present review is to therefore evaluate the current evidence for an effect of SCFAs on whole-body energy expenditure and to assess the potential underlying mechanisms. The available data highlights that SCFAs can exert multiple effects at various organ and tissue sites that would cumulatively raise energy expenditure via a promotion of lipid oxidation. In conclusion, the present review proposes that dietary interventions and other therapies that augment gut-derived SCFAs and systemic availability may present an effective strategy to improve long-term energy balance and body weight management.


Assuntos
Fibras na Dieta/metabolismo , Metabolismo Energético/fisiologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Animais , Peso Corporal/fisiologia , Humanos , Metabolismo dos Lipídeos/fisiologia , Oxirredução , Ganho de Peso/fisiologia
7.
Nutrients ; 11(4)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995824

RESUMO

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.


Assuntos
Apetite/efeitos dos fármacos , Metabolismo Basal/efeitos dos fármacos , Suplementos Nutricionais , Manipulação de Alimentos , Inulina/farmacologia , Obesidade , Propionatos/farmacologia , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Calorimetria Indireta , Colo , Estudos Cross-Over , Método Duplo-Cego , Ingestão de Energia/efeitos dos fármacos , Feminino , Hormônios/sangue , Humanos , Inulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso , Propionatos/uso terapêutico , Descanso , Resposta de Saciedade/efeitos dos fármacos , Paladar
8.
Gut ; 68(8): 1430-1438, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30971437

RESUMO

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 20 g/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, cross-over 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 with cellulose supplementation, measured by homeostatic model assessment 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 proinflammatory interleukin-8 levels compared with cellulose, while 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 Clostridiales) compared with 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.


Assuntos
Microbioma Gastrointestinal/fisiologia , Insulina/metabolismo , Inulina , Metaboloma/fisiologia , Obesidade , Sobrepeso , Adulto , Índice de Massa Corporal , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Fezes/microbiologia , Feminino , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Inulina/administração & dosagem , Inulina/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/dietoterapia , Obesidade/metabolismo , Sobrepeso/diagnóstico , Sobrepeso/dietoterapia , Sobrepeso/metabolismo , Propionatos/administração & dosagem , Propionatos/metabolismo , Resultado do Tratamento
9.
Lancet ; 393(10170): 384-386, 2019 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-30638908
10.
Diabetes Obes Metab ; 21(2): 372-376, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30098126

RESUMO

The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD). Eighteen adults were randomized to receive 20 g/d of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an inulin control for 42 days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between the groups (P = 0.082), however, IHCL significantly increased within the inulin-control group (20.9% ± 2.9% to 26.8% ± 3.9%; P = 0.012; n = 9), which was not observed within the IPE group (22.6% ± 6.9% to 23.5% ± 6.8%; P = 0.635; n = 9). The predominant SCFA from colonic fermentation of inulin is acetate, which, in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate-mediated increase in IHCL.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Voláteis/farmacologia , Inulina/farmacologia , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Propionatos/farmacologia , Adolescente , Adulto , Idoso , Ésteres/farmacologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto Jovem
11.
Curr Nutr Rep ; 7(4): 198-206, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30264354

RESUMO

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.


Assuntos
Bactérias/metabolismo , Doenças Cardiovasculares/microbiologia , Fibras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Fermentação , Microbioma Gastrointestinal , Intestinos/microbiologia , Doenças Metabólicas/microbiologia , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Metabolismo Energético , Nível de Saúde , Interações Hospedeiro-Patógeno , Humanos , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/prevenção & controle , Prognóstico , Medição de Risco , Fatores de Risco
12.
Diabetes Obes Metab ; 20(4): 1034-1039, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29134744

RESUMO

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.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Jejum/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Propionatos/administração & dosagem , Descanso , Administração Oral , Adulto , Metabolismo Basal/efeitos dos fármacos , Feminino , Humanos , Masculino , Oxirredução , Propionatos/farmacologia , Descanso/fisiologia , Adulto Jovem
13.
Lancet Diabetes Endocrinol ; 5(3): 184-195, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28089709

RESUMO

BACKGROUND: 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, the concentrations of which can be affected by food intake. We hypothesised that metabolic profiles of urine samples developed under controlled feeding conditions reflect dietary intake and can be used to model and classify dietary patterns of free-living populations. METHODS: In this randomised, controlled, crossover trial, we recruited healthy volunteers (aged 21-65 years, BMI 20-35 kg/m2) from a database of a clinical research unit in the UK. We developed four dietary interventions with a stepwise variance in concordance with the WHO healthy eating guidelines that aim to prevent non-communicable diseases (increase fruits, vegetables, whole grains, and dietary fibre; decrease fats, sugars, and salt). Participants attended four inpatient stays (72 h each, separated by at least 5 days), during which they were given one dietary intervention. The order of diets was randomly assigned across study visits. Randomisation was done by an independent investigator, with the use of opaque, sealed, sequentially numbered envelopes that each contained one of the four dietary interventions in a random order. Participants and investigators were not masked from the dietary intervention, but investigators analysing the data were masked from the randomisation order. During each inpatient period, urine was collected daily over three timed periods: morning (0900-1300 h), afternoon (1300-1800 h), and evening and overnight (1800-0900 h); 24 h urine samples were obtained by pooling these samples. Urine samples were assessed by proton nuclear magnetic resonance (1H-NMR) spectroscopy, and diet-discriminatory metabolites were identified. We developed urinary metabolite models for each diet and identified the associated metabolic profiles, and then validated the models using data and samples from the INTERMAP UK cohort (n=225) and a healthy-eating Danish cohort (n=66). This study is registered with ISRCTN, number ISRCTN43087333. FINDINGS: Between Aug 13, 2013, and May 18, 2014, we contacted 300 people with a letter of invitation. 78 responded, of whom 26 were eligible and invited to attend a health screening. Of 20 eligible participants who were randomised, 19 completed all four 72 h study stays between Oct 2, 2013, and July 29, 2014, and consumed all the food provided. Analysis of 1H-NMR spectroscopy data indicated that urinary metabolic profiles of the four diets were distinct. Significant stepwise differences in metabolite concentrations were seen between diets with the lowest and highest metabolic risks. Application of the derived metabolite models to the validation datasets confirmed the association between urinary metabolic and dietary profiles in the INTERMAP UK cohort (p<0·0001) and the Danish cohort (p<0·0001). INTERPRETATION: Urinary metabolite models developed in a highly controlled environment can classify groups of free-living people into consumers of diets associated with lower or higher non-communicable disease risk on the basis of multivariate metabolite patterns. This approach enables objective monitoring of dietary patterns in population settings and enhances the validity of dietary reporting. FUNDING: UK National Institute for Health Research and UK Medical Research Council.


Assuntos
Biomarcadores/urina , Dieta , Metaboloma , Metabolômica/métodos , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fenótipo , Adulto Jovem
14.
Diabetes Obes Metab ; 19(2): 257-265, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27761989

RESUMO

AIMS: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on ß-cell function in humans and the direct effects of propionate on isolated human islets in vitro. MATERIALS AND METHODS: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and non-esterified fatty acid (NEFA) levels were quantified pre- and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities. RESULTS: Colonic propionate delivery in vivo was associated with improved ß-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet ß-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines. CONCLUSIONS: Our results indicate that propionate has beneficial effects on ß-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain ß-cell mass through inhibition of apoptosis. These observations support ingestion of propiogenic dietary fibres to maintain healthy glucose homeostasis.


Assuntos
Apoptose/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Propionatos/farmacologia , Receptores de Superfície Celular/efeitos dos fármacos , Adulto , Idoso , Western Blotting , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/efeitos dos fármacos , Caspase 7/metabolismo , Colo , Gorduras na Dieta , Ésteres/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Ácidos Graxos Voláteis , Feminino , Peptídeo 1 Semelhante ao Glucagon/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Inulina/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/metabolismo
15.
Am J Clin Nutr ; 104(1): 5-14, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27169834

RESUMO

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 an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438.


Assuntos
Regulação do Apetite , Colo/metabolismo , Corpo Estriado/metabolismo , Sinais (Psicologia) , Ingestão de Energia , Propionatos/metabolismo , Recompensa , Adulto , Antecipação Psicológica , Apetite , Glicemia/metabolismo , Estudos Cross-Over , Hormônios Gastrointestinais/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Inulina/farmacologia , Masculino , Refeições , Pessoa de Meia-Idade , Vias Neurais , Peptídeo YY/sangue , Resposta de Saciedade
16.
Br J Nutr ; 116(2): 360-74, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27198187

RESUMO

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-ß-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, ß-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.


Assuntos
Apetite/efeitos dos fármacos , Proteínas na Dieta/farmacologia , Ingestão de Energia/efeitos dos fármacos , Proteínas Fúngicas/farmacologia , Hormônios Gastrointestinais/sangue , Insulina/sangue , Obesidade , Adulto , Animais , Apetite/fisiologia , Regulação do Apetite/fisiologia , Proteínas na Dieta/uso terapêutico , Dipeptídeos/sangue , Ingestão de Alimentos/fisiologia , Feminino , Proteínas Fúngicas/uso terapêutico , Fusarium/química , Esvaziamento Gástrico/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/dietoterapia , Obesidade/fisiopatologia , Peptídeo YY/sangue , Período Pós-Prandial , Aves Domésticas , Saciação/efeitos dos fármacos , Adulto Jovem
17.
J Agric Food Chem ; 64(11): 2423-31, 2016 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-26909845

RESUMO

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 by nuclear magnetic resonance spectroscopy as a dose-responsive urinary biomarker of grape intake and subsequently quantified in volunteers following a series of 4-day dietary interventions incorporating 0 g/day, 50 g/day, 100 g/day, and 150 g/day of grapes in standardized diets from a randomized controlled clinical trial. Most accurate quantitative predictions of grape intake were obtained in 24 h urine samples which have the strongest linear relationship between grape intake and tartaric acid excretion (r(2) = 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.


Assuntos
Biomarcadores/urina , Dieta , Frutas , Tartaratos/urina , Vitis , Adulto , Feminino , Frutas/química , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Tartaratos/administração & dosagem
18.
J Appl Physiol (1985) ; 118(11): 1415-22, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25814634

RESUMO

Disturbances in fat oxidation have been associated with an increased risk of obesity and metabolic disorders such as insulin resistance. There is large intersubject variability in the capacity to oxidize fat when a person is physically active, although the significance of this for metabolic health is unclear. We investigated whether the maximal capacity to oxidize fat during exercise is related to 24-h fat oxidation and insulin sensitivity. Maximal fat oxidation (MFO; indirect calorimetry during incremental exercise) and insulin sensitivity (Quantitative Insulin Sensitivity Check Index) were measured in 53 young, healthy men (age 24 ± 7 yr, V̇o2max 52 ± 6 ml·kg(-1)·min(-1)). Fat oxidation over 24 h (24-h FO; indirect calorimetry) was assessed in 16 young, healthy men (age 26 ± 8 yr, V̇o2max 52 ± 6 ml·kg(-1)·min(-1)) during a 36-h stay in a whole-room respiration chamber. MFO (g/min) was positively correlated with 24-h FO (g/day) (R = 0.65, P = 0.003; R = 0.46, P = 0.041 when controlled for V̇o2max [l/min]), 24-h percent energy from FO (R = 0.58, P = 0.009), and insulin sensitivity (R = 0.33, P = 0.007). MFO (g/min) was negatively correlated with 24-h fat balance (g/day) (R = -0.51, P = 0.021) but not significantly correlated with 24-h respiratory quotient (R = -0.29, P = 0.142). Although additional investigations are needed, our data showing positive associations between MFO and 24-h FO, and between MFO and insulin sensitivity in healthy young men suggests that a high capacity to oxidize fat while one is physically active could be advantageous for the maintenance of metabolic health.


Assuntos
Glicemia/metabolismo , Metabolismo Energético , Exercício Físico , Insulina/sangue , Metabolismo dos Lipídeos , Adolescente , Adulto , Biomarcadores/sangue , Calorimetria Indireta , Ingestão de Energia , Teste de Esforço , Voluntários Saudáveis , Humanos , Masculino , Oxirredução , Fatores de Tempo , Adulto Jovem
19.
Proc Nutr Soc ; 74(3): 328-36, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25497601

RESUMO

In recent years, there has been a renewed interest in the role of dietary fibre in obesity management. Much of this interest stems from animal and human studies which suggest that an increased intake of fermentable fibre can suppress appetite and improve weight management. A growing number of reports have demonstrated that the principal products of colonic fermentation of dietary fibre, SCFA, contribute to energy homeostasis via effects on multiple cellular metabolic pathways and receptor-mediated mechanisms. In particular, over the past decade it has been identified that a widespread receptor system exists for SCFA. These G-protein-coupled receptors, free fatty acid receptor (FFAR) 2 and FFAR3 are expressed in numerous tissue sites, including the gut epithelium and adipose tissue. Investigations using FFAR2- or FFAR3-deficient animal models suggest that SCFA-mediated stimulation of these receptors enhances the release of the anorectic hormones peptide tyrosine tyrosine and glucagon-like peptide-1 from colonic L cells and leptin from adipocytes. In addition, the SCFA acetate has recently been shown to have a direct role in central appetite regulation. Furthermore, the SCFA propionate is a known precursor for hepatic glucose production, which has been reported to suppress feeding behaviour in ruminant studies through the stimulation of hepatic vagal afferents. The present review therefore proposes that an elevated colonic production of SCFA could stimulate numerous hormonal and neural signals at different organ and tissue sites that would cumulatively suppress short-term appetite and energy intake.


Assuntos
Regulação do Apetite/fisiologia , Colo/metabolismo , Ingestão de Energia/fisiologia , Ácidos Graxos Voláteis/metabolismo , Animais , Ácidos Graxos Voláteis/biossíntese , Hormônios Gastrointestinais/metabolismo , Glucose/biossíntese , Homeostase/fisiologia , Humanos , Fígado/metabolismo
20.
Gut ; 64(11): 1744-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25500202

RESUMO

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. TRIAL REGISTRATION NUMBER: NCT00750438.


Assuntos
Adiposidade/efeitos dos fármacos , Regulação do Apetite/efeitos dos fármacos , Manutenção do Peso Corporal/efeitos dos fármacos , Colo/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Sobrepeso/tratamento farmacológico , Peptídeo YY/metabolismo , Propionatos/administração & dosagem , Células Cultivadas , Colo/citologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propionatos/farmacologia
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