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Lipidomic techniques can improve our understanding of complex lipid interactions that regulate metabolic diseases. Here, a serum phospholipidomics analysis identified associations between phosphatidylglycerols (PGs) and gut microbiota dysbiosis. Compared with the other phospholipids, serum PGs were the most elevated in patients with low microbiota gene richness, which were normalized after a dietary intervention that restored gut microbial diversity. Serum PG levels were positively correlated with metagenomic functional capacities for bacterial LPS synthesis and host markers of low-grade inflammation; transcriptome databases identified PG synthase, the first committed enzyme in PG synthesis, as a potential mediator. Experiments in mice and cultured human-derived macrophages demonstrated that LPS induces PG release. Acute PG treatment in mice altered adipose tissue gene expression toward remodeling and inhibited ex vivo lipolysis in adipose tissue, suggesting that PGs favor lipid storage. Indeed, several PG species were associated with the severity of obesity in mice and humans. Finally, despite enrichment in PGs in bacterial membranes, experiments employing gnotobiotic mice colonized with recombinant PG overproducing Lactococcus lactis showed limited direct contribution of microbial PGs to the host. In summary, PGs are inflammation-responsive lipids indirectly regulated by the gut microbiota via endotoxins and regulate adipose tissue homeostasis in obesity.-Kayser, B. D., Lhomme, M., Prifti, E., Da Cunha, C., Marquet, F., Chain, F., Naas, I., Pelloux, V., Dao, M.-C., Kontush, A., Rizkalla, S. W., Aron-Wisnewsky, J., Bermúdez-Humarán, L. G., Oakley, F., Langella, P., Clément, K., Dugail, I. Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity.
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Tejido Adiposo/metabolismo , Disbiosis/metabolismo , Inflamación/metabolismo , Obesidad/metabolismo , Fosfatidilgliceroles/metabolismo , Animales , Femenino , Humanos , Lipidómica/métodos , Lipólisis/fisiología , Masculino , Metagenómica/métodos , RatonesRESUMEN
INTRODUCTION: Low gut microbiome richness is associated with dyslipidemia and insulin resistance, and ceramides and other sphingolipids are implicated in the development of diabetes. OBJECTIVES: Determine whether circulating sphingolipids, particularly ceramides, are associated with alterations in the gut microbiome among obese patients with increased diabetes risk. METHODS: This was a cross-sectional and longitudinal retrospective analysis of a dietary/weight loss intervention. Fasted serum was collected from 49 participants (41 women) and analyzed by HPLC-MS/MS to quantify 45 sphingolipids. Shotgun metagenomic sequencing of stool was performed to profile the gut microbiome. RESULTS: Confirming the link to deteriorated glucose homeostasis, serum ceramides were positively correlated with fasting glucose, but inversely correlated with fasting and OGTT-derived measures of insulin sensitivity and ß-cell function. Significant associations with gut dysbiosis were demonstrated, with SM and ceramides being inversely correlated with gene richness. Ceramides with fatty acid chain lengths of 20-24 carbons were the most associated with low richness. Diet-induced weight loss, which improved gene richness, decreased most sphingolipids. Thirty-one MGS, mostly corresponding to unidentified bacteria species, were inversely correlated with ceramides, including a number of Bifidobacterium and Methanobrevibacter smithii. Higher ceramide levels were also associated with increased metagenomic modules for lipopolysaccharide synthesis and flagellan synthesis, two pathogen-associated molecular patterns, and decreased enrichment of genes involved in methanogenesis and bile acid metabolism. CONCLUSION: This study identifies an association between gut microbiota richness, ceramides, and diabetes risk in overweight/obese humans, and suggests that the gut microbiota may contribute to dysregulation of lipid metabolism in metabolic disorders.
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Ceramidas/sangre , Disbiosis/sangre , Glucosa/metabolismo , Metabolómica , Obesidad/sangre , Adulto , Ceramidas/metabolismo , Cromatografía Líquida de Alta Presión , Estudios Transversales , Disbiosis/metabolismo , Femenino , Microbioma Gastrointestinal , Humanos , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Estudios Retrospectivos , Esfingolípidos/sangre , Esfingolípidos/metabolismo , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between faecal A. muciniphila abundance, faecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). DESIGN: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilisation diet in overweight and obese adults (N=49, including 41 women). Faecal A. muciniphila abundance, faecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and weight stabilisation. RESULTS: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. These participants also experienced a reduction in A. muciniphila abundance, but it remained significantly higher than in individuals with lower baseline abundance. A. muciniphila was associated with microbial species known to be related to health. CONCLUSIONS: A. muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults. The interaction between gut microbiota ecology and A. muciniphila warrants further investigation. TRIAL REGISTRATION NUMBER: NCT01314690.
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Dieta Reductora , Heces/microbiología , Microbioma Gastrointestinal , Obesidad/dietoterapia , Verrucomicrobia/aislamiento & purificación , Adulto , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/microbiología , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
PURPOSE OF REVIEW: The role of glycemic index on metabolic and cardiovascular risk factors received considerable attention in light of the current increase in cardiometabolic disorders. We aimed to deal and identify the recently published prospective epidemiological studies as well as randomized controlled studies investigating the associations of metabolic and cardiovascular risk markers with dietary intake of carbohydrates and with measures of the induced glycemic index. The main prospective studies and meta-analysis grouping the recent prospective and clinical interventions are discussed. RECENT FINDINGS: Recently, during the last few years, evidence exists that high glycemic index/glycemic load diets contribute to risk of type 2 diabetes and cardiovascular disease. Additionally, low glycemic index/glycemic load diets were found to be effective in the treatment of cardiometabolic disorders. SUMMARY: The use of the low glycemic index notion in the dietary recommendations for children, adolescents and adults might play a role in the prevention, and or treatment, of metabolic diseases and their cardiovascular complications.
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Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Conducta Alimentaria , Índice Glucémico , Biomarcadores/sangre , Glucemia/metabolismo , Proteína C-Reactiva/metabolismo , Dieta , Homeostasis/fisiología , Humanos , Lípidos/sangre , Metaanálisis como Asunto , Periodo Posprandial , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.
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Consenso , Fibras de la Dieta/normas , Calidad de los Alimentos , Etiquetado de Alimentos , Humanos , Internacionalidad , OrganizacionesRESUMEN
Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/etiología , Dieta/efectos adversos , Índice Glucémico , Carga Glucémica , Adulto , Carbohidratos de la Dieta/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Factores de RiesgoRESUMEN
While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Dieta/efectos adversos , Índice Glucémico , Carga Glucémica , Animales , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Humanos , Incidencia , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
Background: The mechanisms responsible for calorie restriction (CR)-induced improvement in insulin sensitivity (IS) have not been fully elucidated. Greater insight can be achieved through deep biological phenotyping of subjects undergoing CR, and integration of big data. Materials and Methods: An integrative approach was applied to investigate associations between change in IS and factors from host, microbiota, and lifestyle after a 6-week CR period in 27 overweight or obese adults (ClinicalTrials.gov: NCT01314690). Partial least squares regression was used to determine associations of change (week 6 - baseline) between IS markers and lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics of serum, urine and feces, and gut microbiota composition. ScaleNet, a network learning approach based on spectral consensus strategy (SCS, developed by us) was used for reconstruction of biological networks. Results: A spectrum of variables from lifestyle factors (10 nutrients), gut microbiota (10 metagenomics species), and host multi-omics (metabolic features: 84 from serum, 73 from urine, and 131 from feces; and 257 sAT gene probes) most associated with IS were identified. Biological network reconstruction using SCS, highlighted links between changes in IS, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species (MGS). Linear regression analysis to model how changes of select variables over the CR period contribute to changes in IS, showed greatest contributions from gut MGS and fiber intake. Conclusion: This work has enhanced previous knowledge on links between host glucose homeostasis, lifestyle factors and the gut microbiota, and has identified potential biomarkers that may be used in future studies to predict and improve individual response to weight-loss interventions. Furthermore, this is the first study showing integration of the wide range of data presented herein, identifying 115 variables of interest with respect to IS from the initial input, consisting of 9,986 variables. Clinical Trial Registration: clinicaltrials.gov (NCT01314690).
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BACKGROUND: Information is lacking on the potential effect of n-3 polyunsaturated fatty acids (PUFAs) on the adipose tissue of patients with type 2 diabetes. OBJECTIVE: We evaluated whether n-3 PUFAs have additional effects on adiposity, insulin sensitivity, adipose tissue function (production of adipokines and inflammatory and atherogenic factors), and gene expression in type 2 diabetes. DESIGN: Twenty-seven women with type 2 diabetes without hypertriglyceridemia were randomly allocated in a double-blind parallel design to 2 mo of 3 g/d of either fish oil (1.8 g n-3 PUFAs) or placebo (paraffin oil). RESULTS: Although body weight and energy intake measured by use of a food diary were unchanged, total fat mass (P < 0.019) and subcutaneous adipocyte diameter (P < 0.0018) were lower in the fish oil group than in the placebo group. Insulin sensitivity was not significantly different between the 2 groups (measured by homeostasis model assessment in all patients and by euglycemic-hyperinsulinemic clamp in a subgroup of 5 patients per group). By contrast, atherogenic risk factors, including plasma triacylglycerol (P < 0.03), the ratio of triacylglycerol to HDL cholesterol (atherogenic index, P < 0.03), and plasma plasminogen activator inhibitor-1 (P < 0.01), were lower in the fish oil group than in the placebo group. In addition, a subset of inflammation-related genes was reduced in subcutaneous adipose tissue after the fish oil, but not the placebo, treatment. CONCLUSIONS: A moderate dose of n-3 PUFAs for 2 mo reduced adiposity and atherogenic markers without deterioration of insulin sensitivity in subjects with type 2 diabetes. Some adipose tissue inflammation-related genes were also reduced. These beneficial effects could be linked to morphologic and inflammatory changes in adipose tissue. This trial was registered at clinicaltrials.gov as NCT0037.
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Diabetes Mellitus Tipo 2/dietoterapia , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado/administración & dosificación , Resistencia a la Insulina/fisiología , Grasa Subcutánea/efectos de los fármacos , Adipoquinas/genética , Adipoquinas/metabolismo , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Método Doble Ciego , Femenino , Regulación de la Expresión Génica , Humanos , Insulina/sangre , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Inhibidor 1 de Activador Plasminogénico/sangre , Grasa Subcutánea/fisiología , Triglicéridos/sangreRESUMEN
OBJECTIVE: To evaluate whether a 5-week low-glycemic index (LGI) diet versus a high-glycemic index (HGI) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men. RESEARCH DESIGN AND METHODS: In this study, 11 healthy men were randomly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design. RESULTS: The LGI diet resulted in lower postprandial plasma glucose and insulin profiles and areas under the curve (AUCs) than the HGI diet. A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch (AUC, P < 0.05 LGI vs. HGI). These modifications were associated with a decrease in the total fat mass by approximately 700 g (P < 0.05) and a tendency to increase lean body mass (P < 0.07) without any change in body weight. This decrease in fat mass was accompanied by a decrease in leptin, lipoprotein lipase, and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue (P < 0.05). CONCLUSIONS: We concluded that 5 weeks of an LGI diet ameliorates some plasma lipid parameters, decreases total fat mass, and tends to increase lean body mass without changing body weight. These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism. Such a diet could be of benefit to healthy, slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications.
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Glucemia/metabolismo , Leptina/sangre , Lípidos/sangre , Obesidad/dietoterapia , Adulto , Peso Corporal , Estudios Cruzados , Humanos , Insulina/sangre , Leptina/genética , Leptina/metabolismo , Activadores de Lipoproteína Lipasa , Masculino , Persona de Mediana Edad , Obesidad/sangre , Péptidos/genética , Péptidos/metabolismo , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Tiempo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: To determine whether a chronic low-glycemic index (LGI) diet, compared with a high-glycemic index (HGI) diet, has beneficial effects on plasma glucose control, lipid metabolism, total fat mass, and insulin resistance in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twelve type 2 diabetic men were randomly allocated to two periods of 4 weeks of an LGI or HGI carbohydrate diet separated by a 4-week washout interval, in a crossover design. RESULTS: The LGI diet induced lower postprandial plasma glucose and insulin profiles and areas under the curve than after the HGI diet. At the end of the two dietary periods, the 7-day dietary records demonstrated equal daily total energy and macronutrient intake. Body weight and total fat mass were comparable. Four-week LGI versus HGI diet induced improvement of fasting plasma glucose (P < 0.01, Delta changes during LGI vs. HGI), HbA(1c) (P < 0.01), and whole-body glucose utilization measured by the euglycemic-hyperinsulinemic clamp (P < 0.05). LGI diet induced a decrease in fasting plasma total and LDL cholesterol (Delta changes LGI vs. HGI, P < 0.01), free fatty acids (P < 0.01), apolipoprotein B, and plasminogen activator inhibitor 1 activity. CONCLUSIONS: Only 4 weeks of an LGI diet was able to improve glycemic control, glucose utilization, some lipid profiles, and the capacity for fibrinolysis in type 2 diabetes. Even if changes in glycemic control were modest during the 4-week period, the use of an LGI diet in a longer-term manner might play an important role in the treatment and prevention of diabetes and related disorders.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Carbohidratos de la Dieta , Glucosa/metabolismo , Índice Glucémico , Lípidos/sangre , Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Fibrinólisis , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
BACKGROUND: Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. OBJECTIVES: Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. METHODS: In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥ 25 kg/m(2), unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. RESULTS: Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24 ± 0.50 vs +0.12 ± 0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. CONCLUSIONS: Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01530685.
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Glucemia/efectos de los fármacos , Carnosina/administración & dosificación , Cromo/administración & dosificación , Cinnamomum zeylanicum , Obesidad/dietoterapia , Sobrepeso/dietoterapia , Extractos Vegetales/administración & dosificación , Estado Prediabético/dietoterapia , Adulto , Anciano , Glucemia/metabolismo , Composición Corporal/efectos de los fármacos , Cinnamomum zeylanicum/química , Diabetes Mellitus Tipo 2/prevención & control , Suplementos Dietéticos , Método Doble Ciego , Ayuno/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos/anatomía & histología , Músculos/efectos de los fármacos , Músculos/metabolismo , Obesidad/complicaciones , Sobrepeso/complicaciones , Placebos , Estado Prediabético/complicacionesRESUMEN
Low-glycemic index diets are associated with a wide range of benefits when followed on a chronic basis. The chronic effects, however, of the substitution of 1 meal per day are not well known in diabetic subjects. Therefore, we aimed to evaluate whether the chronic use of a low-glycemic index breakfast (low-GIB) rich in low-GI carbohydrates and a modest amount of soluble fibers could have an effect on lipemia at a subsequent lunch, and improve glucose and lipid metabolism in men with type 2 diabetes. A total of 13 men with type 2 diabetes were randomly allocated in a double-blind cross-over design to a 4-week daily intake of a low-GI versus a high-GI breakfast separated by a 15-day washout interval. The low-GI breakfast was composed of whole grain bread and muesli containing 3 g beta-glucan from oats. Low-GIB induced lower postprandial plasma glucose peaks than the high-GIB at the beginning (baseline, P <.001) and after the 4-week intake (P <.001). The incremental area under the plasma glucose curve was also lower (P <.001, P <.01, baseline, and 4 weeks, respectively). There was no effect on fasting plasma glucose, insulin, fructosamine, or glycosylated hemoglobin (HbA(1c)). Fasting plasma cholesterol, as well as the incremental area under the cholesterol curve, were lower (P <.03, P <.02) after the 4-week low-GIB period than after the high-GIB period. Apolipoprotein B (apo B) was also decreased by the 4-week low-GIB. There was no effect of the low-GI breakfast on triacylglycerol excursions or glucose and insulin responses at the second meal. The high-GIB, however, tended to decrease the amount of mRNA of leptin in abdominal adipose tissue, but had no effect on peroxisome proliferator-activated receptor gamma (PPARgamma) and cholesterylester transfer protein (CETP) mRNA amounts. In conclusion, the intake of a low-GI breakfast containing a modest amount (3 g) of beta-glucan for 4 weeks allowed good glycemic control and induced low plasma cholesterol levels in men with type 2 diabetes. The decrease in plasma cholesterol associated with low-GI breakfast intake may reduce the risk of developing cardiovascular complications in subjects with type 2 diabetes.
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Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Carbohidratos de la Dieta/uso terapéutico , Fibras de la Dieta/uso terapéutico , Glicoproteínas , Tejido Adiposo/metabolismo , Adulto , Anciano , Apolipoproteínas B/sangre , Glucemia , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Colesterol/sangre , Proteínas de Transferencia de Ésteres de Colesterol , Estudios Cruzados , Método Doble Ciego , Fructosamina/sangre , Glucosa/metabolismo , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Leptina/genética , Leptina/metabolismo , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Triglicéridos/sangreRESUMEN
BACKGROUND: Associations between dietary patterns, metabolic and inflammatory markers and gut microbiota are yet to be elucidated. OBJECTIVES: We aimed to characterize dietary patterns in overweight and obese subjects and evaluate the different dietary patterns in relation to metabolic and inflammatory variables as well as gut microbiota. DESIGN: Dietary patterns, plasma and adipose tissue markers, and gut microbiota were evaluated in a group of 45 overweight and obese subjects (6 men and 39 women). A group of 14 lean subjects were also evaluated as a reference group. RESULTS: Three clusters of dietary patterns were identified in overweight/obese subjects. Cluster 1 had the least healthy eating behavior (highest consumption of potatoes, confectionary and sugary drinks, and the lowest consumption of fruits that was associated also with low consumption of yogurt, and water). This dietary pattern was associated with the highest LDL cholesterol, plasma soluble CD14 (pâ=â0.01) a marker of systemic inflammation but the lowest accumulation of CD163+ macrophages with anti-inflammatory profile in adipose tissue (pâ=â0.05). Cluster 3 had the healthiest eating behavior (lower consumption of confectionary and sugary drinks, and highest consumption of fruits but also yogurts and soups). Subjects in this Cluster had the lowest inflammatory markers (sCD14) and the highest anti-inflammatory adipose tissue CD163+ macrophages. Dietary intakes, insulin sensitivity and some inflammatory markers (plasma IL6) in Cluster 3 were close to those of lean subjects. Cluster 2 was in-between clusters 1 and 3 in terms of healthfulness. The 7 gut microbiota groups measured by qPCR were similar across the clusters. However, the healthiest dietary cluster had the highest microbial gene richness, as evaluated by quantitative metagenomics. CONCLUSION: A healthier dietary pattern was associated with lower inflammatory markers as well as greater gut microbiota richness in overweight and obese subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01314690.
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Dieta , Intestinos/microbiología , Microbiota , Obesidad/microbiología , Tejido Adiposo/patología , Adulto , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Ingestión de Alimentos , Heces/microbiología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: The most effective and safe dietary approach for weight loss and its impact on the metabolic functions and morphology of adipose tissue remain unclear. OBJECTIVES: We evaluated whether an energy-restricted high-protein diet with a low glycemic index and soluble fiber (LC-P-LGI) would be more effective than a low-calorie conventional diet (LC-CONV) on weight loss and related metabolic risk factors. We further determined factors that may influence adipocyte size during energy restriction. DESIGN: Thirteen obese participants were randomly assigned in a crossover design to 2 periods of a 4-wk hypocaloric diet as either LC-P-LGI or LC-CONV, separated by 8-wk washout intervals. RESULTS: In comparison with the LC-CONV diet, the main effect of the LC-P-LGI diet was a greater decrease in adipocyte diameter (P = 0.048), plasma plasminogen activator inhibitor protein-1 (P = 0.019), vascular endothelial growth factor (P = 0.032), and interferon-γ inducible protein 10 (P = 0.010). Whereas fasting plasma glucose and high-sensitivity C-reactive protein decreased only after the LC-P-LGI diet, with no differences between diets, fasting plasma insulin and insulin resistance were lower after the LC-CONV diet. The diet results did not differ for body composition and lipid variables. Kinetic modifications in adipocyte diameter were associated with metabolic variables and genes implicated in adipocyte proliferation, apoptosis, and angiogenesis. CONCLUSIONS: In comparison with the LC-CONV diet, the LC-P-LGI diet was associated with improvement in some cardiometabolic risk factors and greater reduction in adipocyte size. Profiles of genes involved in inhibiting adipogenesis and angiogenesis, but increasing apoptosis, were correlated with decreased adipocyte size. This study provides insight into the adipose tissue-remodeling changes that induce regulation of adipocyte size during dietary weight loss. This trial was registered at clinicaltrials.gov as NCT01312740.
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Tejido Adiposo/patología , Restricción Calórica , Enfermedades Cardiovasculares/prevención & control , Dieta Reductora , Carbohidratos de la Dieta/administración & dosificación , Proteínas en la Dieta/uso terapéutico , Obesidad/dietoterapia , Adipocitos/fisiología , Adipogénesis/genética , Adipogénesis/fisiología , Tejido Adiposo/citología , Adulto , Glucemia/metabolismo , Proteína C-Reactiva/metabolismo , Quimiocina CXCL10/sangre , Estudios Cruzados , Fibras de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/farmacología , Ingestión de Energía , Femenino , Expresión Génica , Índice Glucémico , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/patología , Inhibidor 1 de Activador Plasminogénico/sangre , Factores de Riesgo , Factor A de Crecimiento Endotelial Vascular , Pérdida de Peso/fisiologíaRESUMEN
This paper reviews evidence in the context of current research linking dietary fructose to health risk markers.Fructose intake has recently received considerable media attention, most of which has been negative. The assertion has been that dietary fructose is less satiating and more lipogenic than other sugars. However, no fully relevant data have been presented to account for a direct link between dietary fructose intake and health risk markers such as obesity, triglyceride accumulation and insulin resistance in humans. First: a re-evaluation of published epidemiological studies concerning the consumption of dietary fructose or mainly high fructose corn syrup shows that most of such studies have been cross-sectional or based on passive inaccurate surveillance, especially in children and adolescents, and thus have not established direct causal links. Second: research evidence of the short or acute term satiating power or increasing food intake after fructose consumption as compared to that resulting from normal patterns of sugar consumption, such as sucrose, remains inconclusive. Third: the results of longer-term intervention studies depend mainly on the type of sugar used for comparison. Typically aspartame, glucose, or sucrose is used and no negative effects are found when sucrose is used as a control group.Negative conclusions have been drawn from studies in rodents or in humans attempting to elucidate the mechanisms and biological pathways underlying fructose consumption by using unrealistically high fructose amounts.The issue of dietary fructose and health is linked to the quantity consumed, which is the same issue for any macro- or micro nutrients. It has been considered that moderate fructose consumption of ≤50g/day or ~10% of energy has no deleterious effect on lipid and glucose control and of ≤100g/day does not influence body weight. No fully relevant data account for a direct link between moderate dietary fructose intake and health risk markers.
RESUMEN
Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD (n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.
Asunto(s)
Grasas Insaturadas en la Dieta/farmacología , Aceites de Pescado/farmacología , Resistencia a la Insulina , Péptidos y Proteínas de Señalización Intercelular/sangre , Leptina/sangre , Obesidad/fisiopatología , Adiponectina , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Tamaño de la Célula , Dieta , Ingestión de Energía/efectos de los fármacos , Expresión Génica , Insulina/sangre , Lípidos/sangre , Hígado/metabolismo , Masculino , Obesidad/sangre , Obesidad/etiología , Obesidad/patología , Ratas , Ratas Wistar , Sacarosa/administración & dosificación , Sacarosa/farmacología , Triglicéridos/metabolismoRESUMEN
The study was designed to evaluate the chronic regulation of plasma leptin by dietary (n-3) polyunsaturated fatty acids (PUFA) in insulin-resistant, sucrose-fed rats. Male Sprague-Dawley rats were randomly assigned to consume for 3 or 6 wk a diet containing 57.5% (g/100 g) sucrose and 14% lipids as either fish oil (SF) or control oils (SC). After 3 and 6 wk of consuming the SF diet, plasma leptin was 70% (P < 0.001) and 75% (P < 0.05) greater, respectively, than in rats fed the SC diet. The same result was found when plasma leptin was adjusted by total fat mass, as measured by dual-energy X-ray absorptiometry. Despite high leptin levels, food intake of rats fed the SF diet was greater than in SC-fed rats without any difference in body weight or total fat mass. After 3 wk, accumulated leptin in epididymal and retroperitoneal adipose tissue was higher in the SF-fed rats than in the SC-fed rats. However, after 6 wk, tissue leptin in the SF-fed rats did not differ from that of the SC-fed rats. The SF diet increased adipose tissue glucose transporter-4 protein quantity and prevented the sucrose-induced elevations in plasma triglycerides and free fatty acids. When all SC- and SF-fed rats (both diets and feeding durations) were considered, plasma leptin levels were positively correlated with body weight (r = 0.5, P < 0.0001) and with total fat mass (r = 0.5, P < 0.0005). These results suggest that plasma leptin at a given time could be inappropriately high for a given fat mass in insulin-sensitive rats fed (n-3) PUFA.