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BACKGROUND/OBJECTIVES: Pre-treatment gut microbial Prevotella-to-Bacteroides (P/B) ratio and markers of glucose metabolism (i.e., fasting glucose and insulin) have been suggested as biomarkers for optimal weight management. However, both biomarkers need further validation, and the interactions between them for optimal weight management are largely unknown. To investigate differences in weight loss maintenance between subjects with low and high P/B ratio and the potential interactions with markers of glucose metabolism and dietary fiber intake. SUBJECTS/METHODS: Following an 8-week weight loss period using meal replacement products, subjects losing ≥ 8% of their initial body weight were randomized to one of three protein supplements or maltodextrin for a 24-week weight maintenance period. Habitual diet was consumed along with the supplements expected to constitute 10-15% of total energy. For this analysis we stratified the participants into low and high strata based on median values of pre-intervention P/B ratio, pre-weight loss Homeostatic model assessment of insulin resistance (HOMA-IR) (<2.33 or > 2.33), and dietary fiber intake during the intervention (< 28.5 or > 28.5 g/10 MJ). RESULTS: Regardless of weight maintenance regimen, subjects with high P/B ratio (n = 63) regained 1.5 (95% CI 0.4, 2.7) kg body weight (P = 0.007) more than subjects with low P/B ratio (n = 63). The regain among subjects with high P/B ratio was particular evident if HOMA-IR was high and dietary fiber intake was low. Consequently, in the high P/B strata, subjects with high HOMA-IR and low fiber intake (n = 17) regained 5.3 (95% CI 3.3, 7.3) kg (P < 0.001) more body weight compared with participants with low HOMA-IR and high fiber intake (n = 16). CONCLUSIONS: Subjects with high P/B ratio were more susceptible to regain body weight compared with subjects with low P/B ratio, especially when dietary fiber intake was low and glucose metabolism was impaired. These observations underline that both the P/B ratio and markers of glucose metabolism should be considered as important biomarkers within personalized nutrition for optimal weight management.
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Resistencia a la Insulina , Pérdida de Peso , Bacteroides , Biomarcadores , Glucemia , Índice de Masa Corporal , Dieta , Glucosa , Humanos , Insulina , Prevotella , PronósticoRESUMEN
BACKGROUND & AIMS: Gut microbiota composition is linked to obesity and metabolic syndrome. The nutrients and doses required to modulate the gut microbiota towards beneficially influence components of the metabolic syndrome are unclear. This study aimed to investigate diet-induced effects on the gut microbiota and metabolic markers in overweight individuals with indices of the metabolic syndrome. METHODS: A twelve-week randomized cross-over trial was conducted with two intervention periods separated by a washout period. The dietary intakes of interest were wheat bran extract, rich in arabinoxylan oligosaccharides (AXOS) (10.4 g/d AXOS) and polyunsaturated fatty acids (PUFA) (3.6 g/d n-3 PUFA). Dietary records, fecal and blood samples, as well as anthropometric data, were collected before and after intervention. Anthropometry and gastrointestinal symptoms were evaluated weekly. Gut microbiota composition was analyzed by massive sequencing of 16S ribosomal RNA gene V3V4 amplicons. RESULTS: Twenty-seven participants completed the study (90%). Intake of AXOS induced an expected bifidogenic effect on gut microbiota (p < 0.01) and increased butyrate-producing bacterial species as well (p < 0.05). Beta-diversity analysis indicated that the structure of the gut microbiota only changed as a result of the AXOS intervention (Permanova = 1.90, p < 0.02) and no changes in metabolic markers were observed after any of the interventions. CONCLUSIONS: AXOS intake has a bifidogenic effect and also increases butyrate producers in the gut microbiota; even though this type of dietary fiber did not modulate lipid or glucose metabolic parameters related to metabolic syndrome. Four-week PUFA intake did not induce any notable effect on the gut microbiota composition or metabolic risk markers. REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT02215343. CLINICAL TRIAL REGISTRATION: Registered at https://www.clinicaltrials.gov/ (NCT02215343). ETHICAL COMMITTEE: H-4-2014-052. THE DANISH DATA PROTECTION AGENCY: 2013-54-0522.
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Fibras de la Dieta/farmacología , Ácidos Grasos Insaturados/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Síndrome Metabólico/metabolismo , Sobrepeso/metabolismo , Xilanos/farmacología , Adolescente , Adulto , Estudios Cruzados , Dieta/métodos , Femenino , Humanos , Masculino , Síndrome Metabólico/microbiología , Persona de Mediana Edad , Oligosacáridos , Sobrepeso/microbiología , Adulto JovenRESUMEN
Long-term consumption of dietary fiber is generally considered beneficial for weight management and metabolic health, but the results of interventions vary greatly depending on the type of dietary fibers involved. This study provides a comprehensive evaluation of the effects of a specific dietary fiber consisting of a wheat-bran extract enriched in arabinoxylan-oligosaccharides (AXOS) in a human intervention trial. An integrated multi-omics analysis has been carried out to evaluate the effects of an intervention trial with an AXOS-enriched diet in overweight individuals with indices of metabolic syndrome. Microbiome analyses were performed by shotgun DNA sequencing in feces; in-depth metabolomics using nuclear magnetic resonance in fecal, urine, and plasma samples; and massive lipid profiling using mass spectrometry in fecal and serum/plasma samples. In addition to their bifidogenic effect, we observed that AXOS boost the proportion of Prevotella species. Metagenome analysis showed increases in the presence of bacterial genes involved in vitamin/cofactor production, glycan metabolism, and neurotransmitter biosynthesis as a result of AXOS intake. Furthermore, lipidomics analysis revealed reductions in plasma ceramide levels. Finally, we observed associations between Prevotella abundance and short-chain fatty acids (SCFAs) and succinate concentration in feces and identified a potential protective role of Eubacterium rectale against metabolic disease given that its abundance was positively associated with plasma phosphatidylcholine levels, thus hypothetically reducing bioavailability of choline for methylamine biosynthesis. The metagenomics, lipidomics, and metabolomics data integration indicates that sustained consumption of AXOS orchestrates a wide variety of changes in the gut microbiome and the host metabolism that collectively would impact on glucose homeostasis. (This study has been registered at ClinicalTrials.gov under identifier NCT02215343)IMPORTANCE The use of dietary fiber food supplementation as a strategy to reduce the burden of diet-related diseases is a matter of study given its cost-effectiveness and the positive results demonstrated in clinical trials. This multi-omics assessment, on different biological samples of overweight subjects with signs of metabolic syndrome, sheds light on the early and less evident effects of short-term AXOS intake on intestinal microbiota and host metabolism. We observed a deep influence of AXOS on gut microbiota beyond their recognized bifidogenic effect by boosting concomitantly a wide diversity of butyrate producers and Prevotella copri, a microbial species abundant in non-Westernized populations with traditional lifestyle and diets enriched in fresh unprocessed foods. A comprehensive evaluation of hundreds of metabolites unveiled new benefits of the AXOS intake, such as reducing the plasma ceramide levels. Globally, we observed that multiple effects of AXOS consumption seem to converge in reversing the glucose homeostasis impairment.
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BACKGROUND/OBJECTIVES: Individuals with high pre-treatment bacterial Prevotella-to-Bacteroides (P/B) ratio have been reported to lose more body weight on diets high in fiber than subjects with a low P/B ratio. Therefore, the aim of the present study was to examine potential differences in dietary weight loss responses between participants with low and high P/B. SUBJECTS/METHODS: Eighty overweight participants were randomized (52 completed) to a 500 kcal/d energy deficit diet with a macronutrient composition of 30 energy percentage (E%) fat, 52 E% carbohydrate and 18 E% protein either high (≈1500 mg calcium/day) or low ( ≤ 600 mg calcium/day) in dairy products for 24 weeks. Body weight, body fat, and dietary intake (by 7-day dietary records) were determined. Individuals were dichotomized according to their pre-treatment P/B ratio derived from 16S rRNA gene sequencing of collected fecal samples to test the potential modification of dietary effects using linear mixed models. RESULTS: Independent of the randomized diets, individuals with high P/B lost 3.8 kg (95%CI, 1.8,5.8; P < 0.001) more body weight and 3.8 kg (95% CI, 1.1, 6.5; P = 0.005) more body fat compared to individuals with low P/B. After adjustment for multiple covariates, individuals with high P/B ratio lost 8.3 kg (95% CI, 5.8;10.9, P < 0.001) more body weight when consuming above compared to below 30 g fiber/10MJ whereas this weight loss was 3.2 kg (95% CI, 0.8;5.5, P = 0.008) among individuals with low P/B ratio [Mean difference: 5.1 kg (95% CI, 1.7;8.6, P = 0.003)]. Partial correlation coefficients between fiber intake and weight change was 0.90 (P < 0.001) among individuals with high P/B ratio and 0.25 (P = 0.29) among individuals with low P/B ratio. CONCLUSIONS: Individuals with high P/B lost more body weight and body fat compared to individuals with low P/B, confirming that individuals with a high P/B are more susceptible to weight loss on a diet rich in fiber.
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Bacteroides/fisiología , Heces/microbiología , Microbioma Gastrointestinal/fisiología , Nutrientes/administración & dosificación , Sobrepeso/dietoterapia , Prevotella/fisiología , Pérdida de Peso/fisiología , Adulto , Dieta Reductora , Fibras de la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sobrepeso/metabolismo , Sobrepeso/microbiología , ARN Ribosómico 16S , Estudios RetrospectivosRESUMEN
BACKGROUND: Obesity is associated with vitamin insufficiency and low grade inflammation. The purpose of this study was to investigate the effect of weight loss on folate, retinol, vitamin B12, D and E status and the degree of inflammation. METHODS: Out of 110, 85 individuals (75% women) aged 39 ± 11 years with a mean ± SD BMI of 33 ± 4 kg/m2, completed an eight-week low energy diet (LED). Serum concentration of folate, retinol, B12, D and E and C-reactive protein and homocysteine (Hcy) were measured at baseline and at end of the LED. RESULTS: At baseline, 8% of the participants were deficient in folate, 13% in vitamin B12, 2% in retinol, 28% in vitamin D (72% were insufficient in vitamin D), and none were deficient in vitamin E. At baseline, BMI was inversely associated with retinol (P < 0.05) as was total and abdominal fat percentage with folate (P < 0.05); further BMI and measures of adiposity were positively associated with CRP (P < 0.01) and Hcy (P < 0.05). Homocysteine was inversely associated with all vitamins but retinol (P < 0.001). After the LED, the participants lost a mean [95% confidence intervals] of 12.3 [- 13.1,-11.6] kg. The serum concentration of folate, vitamin B12 and D were increased (P < 0.001) after the LED whereas the concentration of retinol and vitamin E were reduced (P < 0.001). CONCLUSION: Eight-weeks LED resulted in 13% weight loss and an increase in the serum concentrations of folate, vitamin B12 and D. Baseline adiposity was inversely associated with folate and retinol, and positively associated with markers of inflammation. TRIAL REGISTRATION: Ethical Committee of Copenhagen as no. H-4-2013-135, NCT01561131.
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The aim of the present study was to investigate the associations between the habitual Ca intake and faecal fat and energy excretion as well as blood lipid profile in free-living normal-weight and overweight individuals. The participants were enrolled for an 8-d period where data from a 7-d diet registration (days 1-7), a 5-d faeces collection (days 3-7), a 2-d urine collection (days 5-7), and anthropometric measurements and a fasting blood sample (day 8) were collected. Analyses showed that dietary Ca intake (g/10 MJ per d) was positively associated with excretion of faecal fat (P = 0·004) and energy (P = 0·031) when adjusted for BMI, age, sex and intake of Ca-containing supplements. However, after adjustment for intake of fibre, the effect of Ca intake disappeared. Nevertheless, total cholesterol (CHOL) and LDL-CHOL concentrations were associated negatively with Ca intake (ß -0·62 (95 % CI -0·96, -0·28) mmol/l, P < 0·001, and ß -0·49 (95 % CI -0·78, -0·20) mmol/l, P = 0·001, respectively, per 1000 mg/10 MJ per d increase in Ca intake). In conclusion, incorporation of Ca-rich food products in a habitual diet was associated with reduced total CHOL and LDL-CHOL concentrations, which may lower the risk of CVD in the long term.
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In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of -5·8 to -10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (P interaction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed.
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Alelos , Genotipo , Polimorfismo de Nucleótido Simple , Estaciones del Año , Rayos Ultravioleta , Deficiencia de Vitamina D/genética , Vitamina D/análogos & derivados , Niño , Colestanotriol 26-Monooxigenasa/genética , Familia 2 del Citocromo P450/genética , Dinamarca , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Receptores de Calcitriol/genética , Instituciones Académicas , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Proteína de Unión a Vitamina D/genéticaRESUMEN
We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD) on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA). A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO) and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study.
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Calcio de la Dieta/administración & dosificación , Restricción Calórica , Productos Lácteos , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Espectroscopía de Resonancia Magnética , Metabolómica/métodos , Sobrepeso/dietoterapia , Adulto , Análisis de Varianza , Biomarcadores/sangre , Biomarcadores/orina , Calcio de la Dieta/efectos adversos , Grasas de la Dieta/efectos adversos , Proteínas en la Dieta/efectos adversos , Heces/química , Femenino , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Humanos , Persona de Mediana Edad , Valor Nutritivo , Sobrepeso/diagnóstico , Sobrepeso/metabolismo , Sobrepeso/microbiología , Factores de Tiempo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment.
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Dieta , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Enfermedades Metabólicas/prevención & control , Obesidad/prevención & control , Prebióticos , Animales , Humanos , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/microbiología , Obesidad/etiología , Obesidad/microbiologíaRESUMEN
Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague-Dawley rats were fed a diet containing 20% milk powder with different proportions of this being given as heated milk powder (0, 40 or 100%), either native (HMW) or hydrolysed (LMW). Gene expression of RAGE and AGER1 in whole blood increased in the group receiving a high AGE LMW diet, which also had the highest urinary excretion of the AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1). Urinary excretion of N ε-carboxymethyl-lysine increased with increasing proportion of heat-treated milk powder in the HMW and LMW diets but was unrelated to gene expression. There was no difference in insulin sensitivity, F2-isoprostaglandins, food intake, water intake, body weight or body composition between the groups. In conclusion, RAGE and AGER1 expression can be influenced by a high AGE diet after only 2 weeks in proportion to MG-H1 excretion. No other short-term effects were observed.
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Dieta/efectos adversos , Productos Finales de Glicación Avanzada/efectos adversos , Hexosiltransferasas/metabolismo , Receptor para Productos Finales de Glicación Avanzada/agonistas , Regulación hacia Arriba , Animales , Biomarcadores/sangre , Biomarcadores/orina , Ingestión de Energía , Productos Finales de Glicación Avanzada/administración & dosificación , Productos Finales de Glicación Avanzada/química , Productos Finales de Glicación Avanzada/orina , Hexosiltransferasas/sangre , Hexosiltransferasas/química , Hexosiltransferasas/genética , Calor/efectos adversos , Imidazoles/orina , Imidazolinas/orina , Lisina/análogos & derivados , Lisina/orina , Masculino , Proteínas de la Leche/administración & dosificación , Proteínas de la Leche/efectos adversos , Proteínas de la Leche/química , Peso Molecular , Proteolisis , Distribución Aleatoria , Ratas Sprague-Dawley , Receptor para Productos Finales de Glicación Avanzada/sangre , Receptor para Productos Finales de Glicación Avanzada/genética , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Eliminación Renal , Pruebas de Toxicidad Subaguda , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.
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The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of either L. paracasei F19 (9.4 × 1010 colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (P< 0.05) and improved insulin sensitivity measured by Matsuda index (P< 0.05). Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species (P< 0.01), including decreased relative abundance of eight Faecalibacterium species. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species.
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Dieta , Lino , Intestinos/microbiología , Obesidad/microbiología , Posmenopausia , Probióticos/uso terapéutico , Anciano , Péptido C/sangre , Heces/microbiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Lactobacillus , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Mucílago de Planta/administración & dosificación , Prebióticos , Método Simple CiegoRESUMEN
BACKGROUND: Breakfast is associated with lower body weight in observational studies. Public health authorities commonly recommend breakfast consumption to reduce obesity, but the effectiveness of adopting these recommendations for reducing body weight is unknown. OBJECTIVE: We tested the relative effectiveness of a recommendation to eat or skip breakfast on weight loss in adults trying to lose weight in a free-living setting. DESIGN: We conducted a multisite, 16-wk, 3-parallel-arm randomized controlled trial in otherwise healthy overweight and obese adults [body mass index (in kg/m²) between 25 and 40] aged 20-65 y. Our primary outcome was weight change. We compared weight change in a control group with weight loss in experimental groups told to eat breakfast or to skip breakfast [no breakfast (NB)]. Randomization was stratified by prerandomization breakfast eating habits. A total of 309 participants were randomly assigned. RESULTS: A total of 283 of the 309 participants who were randomly assigned completed the intervention. Treatment assignment did not have a significant effect on weight loss, and there was no interaction between initial breakfast eating status and treatment. Among skippers, mean (±SD) baseline weight-, age-, sex-, site-, and race-adjusted weight changes were -0.71 ± 1.16, -0.76 ± 1.26, and -0.61 ± 1.18 kg for the control, breakfast, and NB groups, respectively. Among breakfast consumers, mean (±SD) baseline weight-, age-, sex-, site-, and race-adjusted weight changes were -0.53 ± 1.16, -0.59 ± 1.06, and -0.71 ± 1.17 kg for the control, breakfast, and NB groups, respectively. Self-reported compliance with the recommendation was 93.6% for the breakfast group and 92.4% for the NB group. CONCLUSIONS: A recommendation to eat or skip breakfast for weight loss was effective at changing self-reported breakfast eating habits, but contrary to widely espoused views this had no discernable effect on weight loss in free-living adults who were attempting to lose weight.
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Desayuno , Dieta Reductora , Conducta Alimentaria , Obesidad/dietoterapia , Sobrepeso/dietoterapia , Educación del Paciente como Asunto , Adulto , Anciano , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Promoción de la Salud , Humanos , Masculino , Persona de Mediana Edad , Política Nutricional , Ciencias de la Nutrición/educación , Cooperación del Paciente , Autoinforme , Pérdida de Peso , Adulto JovenRESUMEN
PURPOSE: Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress. METHODS: In total, 19 healthy overweight individuals completed a crossover meal test with two meals of identical ingredients prepared by roasting (H-AGE) or steaming (L-AGE), respectively. Postprandial blood samples were analysed for N(ε)-carboxymethyl-lysine (CML), appetite-regulating gut hormones, glucose, insulin, triacylglycerol, and markers of inflammation and endothelial activation. Subjective appetite ratings and subsequent food intake were also assessed, and urine was analysed for CML, methylglyoxal-derived hydroimidazolone (MG-H1), and F2-isoprostanes. RESULTS: CML content of the H- and L-AGE meals was 5.0 and 2.8 mg, respectively. Plasma CML and urinary CML and MG-H1 tended to be higher after the H-AGE meal. There was no change in subsequent food intake, appetite sensations, or appetite hormone responses between meals, except for the overall ghrelin response, which was higher after the H-AGE meal compared with the L-AGE meal (p = 0.016). There was an increased glycaemic response to the H-AGE meal (p = 0.027) compared with the L-AGE meal. Inflammatory and endothelial activation markers did not differ between meals, but there was an overall effect on endothelial activation (p = 0.021) and on the oxidative marker, F2-isoprostanes, in urine (p = 0.013). CONCLUSION: The present study did not show any pronounced effects of AGEs on appetite and markers of inflammation, but did indicate that AGEs may affect postprandial ghrelin, oxidative stress, and glucose responses.
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Apetito/efectos de los fármacos , Dieta , Endotelio/fisiología , Productos Finales de Glicación Avanzada/administración & dosificación , Inflamación , Sobrepeso/fisiopatología , Adulto , Glucemia/análisis , Índice de Masa Corporal , Estudios Cruzados , Endotelio/efectos de los fármacos , Ingestión de Energía , F2-Isoprostanos/orina , Femenino , Ghrelina/sangre , Péptido 1 Similar al Glucagón/sangre , Calor , Humanos , Insulina/sangre , Lisina/análogos & derivados , Lisina/sangre , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Péptido YY/sangre , Periodo Posprandial , Vapor , Triglicéridos/sangreRESUMEN
BACKGROUND: TFAP2B rs987237 is associated with obesity and has shown interaction with the dietary fat-to-carbohydrate ratio, which has an effect on weight loss. We investigated interactions between rs987237 and protein-to-carbohydrate ratio or glycemic index (GI) in relation to weight maintenance after weight loss. METHODS: This study included 742 obese individuals from 8 European countries who participated in the Diet, Obesity, and Genes (DiOGenes) trial, lost ≥ 8% of their initial body weight during an 8-week low-calorie diet and were randomized to one of 5 ad libitum diets with a fixed energy percentage from fat: either low-protein/low-GI, low-protein/high-GI, high-protein/low-GI, or high-protein/high-GI diets, or a control diet for a 6-month weight maintenance period. Using linear regression analyses and additive genetic models, we investigated main and dietary interaction effects of TFAP2B rs987237 in relation to weight maintenance. RESULTS: In total, 468 completers of the trial were genotyped for rs987237. High-protein diets were beneficial for weight maintenance in the AA genotype group (67% of participants), but in the AG and GG groups no differences were observed for low- or high-protein diets. On the high-protein diet, carriers of the obesity risk allele (G allele) regained 1.84 kg (95% CI: 0.02; 3.67, p = 0.047) more body weight per risk allele than individuals on a low-protein diet. There was no interaction effect between rs987237 and GI on weight maintenance. CONCLUSION: TFAP2B rs987237 and dietary protein/carbohydrate interacted to modify weight maintenance. Considering the carbohydrate proportion of the diet, the interaction was different from the previously reported rs987237-fat-to-carbohydrate ratio interaction for weight loss. Thus, TFAP2B-macronutrient interactions might diverge depending on the nutritional state.
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Proteínas en la Dieta/metabolismo , Índice Glucémico/genética , Factor de Transcripción AP-2/genética , Pérdida de Peso/genética , Adulto , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Ingesta Diaria RecomendadaRESUMEN
BACKGROUND: Infant docosahexaenoic acid (DHA) status is supported by the DHA content of breast milk and thus can decrease once complementary feeding begins. Furthermore, it is unclear to what extent endogenous DHA synthesis contributes to status. OBJECTIVE: We investigated several determinants, including FADS genotypes on DHA status at 9 mo and 3 y. DESIGN: This was a cross-sectional study with Danish infants from 2 prospective studies [Essentielle Fedtsyrer i OvergangskosteN (EFiON) and the Småbørns Kost Og Trivsel (SKOT) cohort] in which we measured red blood cell (RBC) DHA status at 9 mo (n = 409) and 3 y (n = 176) and genotyped 4 FADS tag single nucleotide polymorphisms (SNPs): rs3834458, rs1535, rs174575, and rs174448 (n = 401). Information about breastfeeding was obtained by using questionnaires, and fish intake was assessed by using 7-d precoded food diaries. RESULTS: FADS genotype, breastfeeding, and fish intake explained 25% of the variation in infant RBC DHA status [mean ± SD: 6.6 ± 1.9% of fatty acids (FA%)]. Breastfeeding explained most of the variation (â¼20%), and still being breastfed at 9 mo was associated with a 0.7 FA% higher DHA compared with no longer being breastfed (P < 0.001). The FADS SNPs rs1535 and rs3834458 were highly correlated (r = 0.98). Homozygous carriers of the minor allele of rs1535 had a DHA increase of 1.8 FA% (P = 0.001) relative to those with the wild-type allele, whereas minor allele carriers of rs174448 and rs174575 had a decrease of 1.1 FA% (P = 0.005) and 2.0 FA% (P = 0.001), respectively. Each 10-g increment in fish intake was associated with an increased DHA status of 0.3 FA%. At 3 y, fish intake was the only significant determinant of DHA status (0.2 FA%/10 g). CONCLUSION: Breastfeeding, FADS genotype, and fish intake are important determinants of DHA status in late infancy. The EFiON study was registered at clinicaltrials.gov as NCT 00631046.
Asunto(s)
Dieta , Ácidos Docosahexaenoicos/sangre , Ácido Graso Desaturasas/genética , Población Blanca/genética , Alelos , Animales , Lactancia Materna , Preescolar , Estudios Transversales , delta-5 Desaturasa de Ácido Graso , Dinamarca , Registros de Dieta , Ácidos Docosahexaenoicos/administración & dosificación , Ingestión de Energía , Eritrocitos/química , Femenino , Peces , Haplotipos , Humanos , Lactante , Modelos Lineales , Masculino , Leche Humana/química , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y CuestionariosRESUMEN
Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene-diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP-diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect) ,and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP-dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of 20.26 mmol/l per A-allele/protein unit (95% CI 20.38, 20.14, P=0.000043). In conclusion, we investigated SNP-diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.
Asunto(s)
Proteínas en la Dieta/metabolismo , Índice Glucémico/fisiología , Metabolismo de los Lípidos/fisiología , Lípidos/sangre , Polimorfismo de Nucleótido Simple , Factor de Transcripción Activador 6/genética , Factor de Transcripción Activador 6/metabolismo , Adulto , HDL-Colesterol/genética , HDL-Colesterol/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Humanos , Metabolismo de los Lípidos/genética , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , Masculino , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Fosfatidato Fosfatasa/genética , Fosfatidato Fosfatasa/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. DESIGN: In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. RESULTS: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. CONCLUSION: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.
Asunto(s)
Conducta Alimentaria , Obesidad/prevención & control , Polimorfismo de Nucleótido Simple/genética , Aumento de Peso/genética , Adulto , Índice de Masa Corporal , Restricción Calórica/métodos , ADN/genética , ADN/aislamiento & purificación , Proteínas en la Dieta/administración & dosificación , Femenino , Sitios Genéticos , Genotipo , Índice Glucémico/genética , Humanos , Masculino , Persona de Mediana Edad , Obesidad/genética , Circunferencia de la Cintura , Pérdida de Peso/genéticaRESUMEN
BACKGROUND: The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27+/-4 kg/m(2)) versus non-carriers (mean BMI: 28+/-5 kg/m(2)) (p>0.05) could be shown. CONCLUSIONS/SIGNIFICANCE: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.
Asunto(s)
Estudios de Asociación Genética , Variación Genética , Obesidad/genética , Receptores de Ghrelina/genética , Dinamarca , Salud de la Familia , Sitios Genéticos , Humanos , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Sobrepeso/genética , Mutación Puntual , Regiones Promotoras Genéticas/genética , Población BlancaRESUMEN
BACKGROUND: Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common known cause of monogenic human obesity. AIMS: The aims of this study were the following: 1) to estimate the prevalence of MC4R mutations in obese Czech children; 2) to evaluate phenotypic features of the mutation carriers; 3) to compare weight, height, and body mass index of MC4R mutation carriers with noncarriers in longitudinal studies; 4) to determine the effect of a weight management program among MC4R mutation carriers; and 5) to perform a functional analysis of a novel variant. SUBJECTS AND METHODS: We analyzed the coding region of MC4R in a cohort of 289 Czech children and adolescents with early-onset obesity by direct sequencing. Information on weight, height, body mass index, baseline biochemical data, and a weight loss follow-up study was obtained. In vitro functional analysis of one novel variant was performed. RESULTS: We identified six different mutations in seven probands: one novel missense mutation Cys84Arg and five previously reported variants, Arg7Cys, Ser19fsdelA, Phe51Leu, Ser127Leu, and Gly181Asp. The Gly181Asp variant was detected in one homozygous carrier from unrelated parents. None of the mutation carriers fulfilled the MC4R syndrome criteria. A comparison of anthropometrics in mutation carriers and noncarriers during 13 yr of follow-up did not reveal any significant differences. MC4R mutation carriers exhibited a similar ability to lose weight as obese noncarriers. The novel variant Cys84Arg showed a significant reduction in cAMP signal properties of the MC4R. CONCLUSIONS: Among obese Czech children, we found a prevalence of 2.4% of MC4R homozygous and heterozygous mutations and showed a similar response to diet management of MC4R mutation carriers and noncarriers.