Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men

Objective: Six lean (BMI = 20.8 ± 0.7) and seven overweight (BMI = 30.8 ± 1.7) young men (18–27 years old) were studied to investigate the acute effect of a high-carbohydrate meal on leptin levels and its relation to energy expenditure as well as to protein, carbohydrate and fat oxidation. Methods: Study participants were given a high-carbohydrate meal (17% as protein, 80% as carbohydrates and 3% as lipids) covering 40% of their estimated daily energy requirements. Serum leptin, insulin, glucose, free fatty acids and triglycerides levels were measured before meal intake and during the four postprandial hours. Furthermore, energy expenditure (EE), protein, carbohydrate and lipid oxidation were measured in fasted and fed conditions. Results: Fasting leptin was found to be positively correlated with circulating insulin concentrations (r = .748; p = 0.011) and body fat in kg (r = .827; p = 0.001). During the measured postprandial period no statistically significant changes were found in leptin levels as compared with pre-meal values in either lean or overweight men, nor differences in leptin changes between both groups. After load intake, carbohydrate oxidation was lower in overweight individuals (p < 0.05), while no significant differences were observed in protein oxidation. Cumulative lipid oxidation was found to be negatively associated with post-meal leptin values, being significantly lower in the overweight as compared with lean men (p < 0.05). This study demonstrates that the acute postprandial fuel substrate utilization is altered in overweight men with a lower carbohydrate oxidation and a strong inhibition of lipid oxidation, which could be attributed to some leptin resistance. Conclusion: These data also suggest that short-term meal-related metabolic responses may explain the long-term body adiposity if they are sustained over long intervals

Thermogenesis induced by a high-carbohydrate meal in fasted lean and overweight young men: insulin, body fat, and sympathetic nervous system involvement

Objective This dietary trial was designed to evaluate the effect of an experimental short-term fasting period followed by a high-carbohydrate meal on energy expenditure, thermogenesis, and sympathetic nervous system activity in normal (body mass index 27 kg/m2) men who were healthy, non-diabetic or with no other endocrine disease, non-smokers, not taking oral prescription medications, and with a stable body weight for the previous 3 mo. Methods Fasting and fed energy expenditures and diet-induced thermogenesis were measured after a high-carbohydrate meal in seven overweight and six lean young male subjects by indirect calorimetry. Heart rate, urinary excretion of catecholamines, serum glucose, and insulin were also measured over the experimental fasting (7.5 h) and postprandial (4 h) periods. Results After carbohydrate intake, overweight men showed a significantly higher energy production (kJ/kg of fat-free mass) than did lean individuals, and the diet-induced thermogenesis (percentage of energy intake) was positively correlated with body fat (kg), percentage of body fat, fat-free mass (kg), and fasting pre-meal serum insulin levels. Postprandial cumulative energy expenditure was directly associated with postprandial insulin response and with mean postprandial heart rate values. No significant differences in urinary catecholamines were found between lean and overweight men at basal conditions or during the study period. Conclusions Overweight individuals showed similar short-term sympathetic nervous system responses induced by an experimental fasting period. Although diet-induced thermogenesis after carbohydrate intake was not statistically different between lean and overweight men, the postprandial insulin response and body fat content seemed to be involved in sympathetic nervous system activity

Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men

BACKGROUND: Adjustments of carbohydrate intake and oxidation occur in both normal-weight and overweight individuals. Nevertheless, the contribution of carbohydrates to the accumulation of fat through either reduction of fat oxidation or stimulation of fat synthesis in obesity remains poorly investigated. OBJECTIVE: The objective of this study was to assess the postprandial metabolic changes and the fractional hepatic de novo lipogenesis (DNL) induced by a high-carbohydrate, low-fat meal in lean and overweight young men. DESIGN: A high-carbohydrate, low-fat meal was administered to 6 lean and 7 overweight men after a 17.5-h fast. During the fasting and postprandial periods, energy expenditure (EE), macronutrient oxidation, diet-induced thermogenesis, and serum insulin, glucose, triacylglycerol, and fatty acids were measured. To determine DNL, [1-13C]sodium acetate was infused and the mass isotopomer distribution analysis method was applied. RESULTS: After intake of the high-carbohydrate meal, the overweight men had hyperinsulinemia and higher fatty acid and triacylglycerol concentrations than did the lean men. The overweight group showed a greater EE, whereas there was no significant difference in carbohydrate oxidation between the groups. Nevertheless, the overweight men had a marginally higher protein oxidation and a lower lipid oxidation than did the lean men. DNL was significantly higher before and after meal intake in the overweight men and was positively associated with fasting serum glucose and insulin concentrations. Furthermore, postprandial DNL was positively correlated with body fat mass, EE, and triacylglycerol. CONCLUSION: After a high-carbohydrate, low-fat meal, overweight men had a lower fat oxidation and a higher fractional hepatic fat synthesis than did lean men

Validación del índice de masa corporal auto-referido en la Encuesta Nacional de Salud

Objective. To assess the validity of self-reported body mass index in the National Health Survey. 120 participants were selected and questioned about their weight and height with exactly the same questions that the National Health Survey uses. Afterwards, and once informed consent was obtained, participants were weighed and measured, and this data was used as the gold standard. On average, participants underestimated their weight by 1.39 kg, overestimated their height by 0.55 cm and underestimated their body mass index by 0.71 kg/m2. The sensitivity of self-reported self reported body mass index (BMI) to detect overweight was 77%, the specificity was 97%, the positive predictive value was 0.95 and the negative predictive value was 0.86. The Kappa index was 0.76 and the quadratically weighted Kappa index was 0.85. The correlation coefficient between self-reported and measured BMI was 0.96 and the intraclass correlation coefficient was 0.97. Self-reported data is an efficient way of obtaining information about BMI, although with limitations, because self-reported data tends to underestimate weight and overestimate height, thus underestimating BMI and the proportion of participants with elevated BMI

A novel nonsense mutation in the melanocortin-4 receptor associated with obesity in a Spanish population

BACKGROUND: In recent years, several groups have reported dominant inheritance of obesity conferred by missense, nonsense and frameshift mutations in the melanocortin 4 receptor gene (MC4R). Hence, MC4R is involved in the most common monogenic form of human obesity described so far. OBJECTIVES: In this context, we screened a Spanish population, composed of obese subjects and normal weight controls, for mutations in the MC4-R by single-strand conformational polymorphism (SSCP). SUBJECTS AND METHODS: Overall 313 individuals, 159 obese subjects (body mass index: BMI: 37.6 kg/m2, 95% CI: 36.7–38.5 kg/m2) and 154 normal weight control subjects (BMI: 22.3 kg/m2, 95% CI: 22.0–22.6 kg/m2) were screened for MC4-R mutations. RESULTS: We detected a novel nonsense mutation at codon 16 of the MC4-R in an obese female (BMI: 30.0 kg/m2) and a previously described missense mutation (Val-253-Ile) located within the sixth trans-membrane domain of the MC4-R in a normal weight individual (BMI: 19.0 kg/m2). The polymorphism Val-103-Ile was detected in one obese individual, while four subjects (two cases and two controls) with the polymorphism Ile-251-Leu were found. CONCLUSIONS: We have identified a novel nonsense mutation (Trp-16-Stop) that, based on previously described frameshift and nonsense mutations, most likely results in dominantly inherited obesity. Within this Spanish population, the frequency of the Ile-251-Leu polymorphism of the MC4R was similar in obese and control subjects (about 1.3%), while the polymorphism Val-103-Ile was only detected in an obese individual (0.6%)

Influencia del polimorfismo -3826 A Æ G en el gen de la UCP1 sobre los componentes del síndrome metabólico

Fundamento. La proteína desacoplante UCP1 se ha relacionado con el desarrollo y/o mantenimiento de la obesidad a través de su implicación en la regulación del balance energético. El papel de esta proteína mitocondrial en humanos es incierto por la escasa presencia del tejido adiposo pardo en el individuo adulto. El polimorfismo -3826 A/G de la UCP1 solo o conjuntamente con la mutación Trp64Arg del receptor adrenérgico β3 se ha asociado con obesidad, diabetes mellitus y enfermedades relacionadas aunque con resultados contradictorios. Con objeto de conocer la influencia del polimorfismo -3826 A/G de la UCP1 sobre los componentes clásicos del síndrome metabólico en nuestra población, se han estudiado 159 individuos obesos y 154 en normopeso, con un diseño de casos y controles. A todos ellos se les ha determinado IMC, índice cintura/cadera, % de grasa corporal, TA, perfil lipídico, leptina, glucemia e insulinemia basales. Asimismo se les ha analizado la presencia de la mencionada mutación en el gen de la UCP1. Resultados. Se obtuvieron diferencias significativas en todas las variables estudiadas entre obesos (casos) y normopeso (controles) Dentro del grupo de obesos, el polimorfismo –3826 A/G del gen de la UCP1 (n=53) se asoció con un mayor IMC (p=0,03), mayor % de grasa corporal (p=0,04) y TA más elevada tanto sistólica (p=0,009) como diastólica (p=0,02) No hubo diferencias estadísticamente significativas en ninguno de los demás índices evaluados. Conclusión. El factor fundamental que influye sobre los componentes del síndrome metabólico es la obesidad. No obstante, el polimorfismo –3826 A/G del gen de la UCP1 se asocia con un mayor grado de obesidad y unas cifras más elevadas de TA

Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism.

Interindividual differences in the response to dietary intake are, in some cases, genotype dependent. Moreover, genotype-environment interactions may appear when the impact of lifestyle factors (e.g., diet) on a phenotype (e.g., BMI > 30 kg/m2) differs by genotype. A case-control study (obese subjects vs. normal weight controls) was conducted to assess a possible effect modification on obesity risk of the Gln27Glu polymorphism for the ß2-adrenoceptor gene depending on dietary intake. The sample included 159 subjects with BMI > 30 kg/m2 and 154 controls with BMI 49% energy (E)] had a higher obesity risk (OR = 2.56, P = 0.051). The product-term introduced in the logistic model to assess effect modification revealed a marginally significant interaction (P = 0.058) between both factors. Furthermore, a high intake of CHO (E > 49%) was associated with higher insulin levels among women carrying the Gln27Glu polymorphism (P < 0.01). This gene-nutrient interaction emphasizes the importance of examining the outcome of some obesity-related mutations depending on lifestyle (including diet) and may explain the heterogeneity of findings from previous studies

Effect of smoking on body weight: longitudinal analysis of the SUN cohort

Our aim was to investigate prospectively the association between two major cardiovascular risk factors: smoking and weight gain. METHODS: We prospectively evaluated 7565 individuals taking part in a dynamic cohort study over a median follow-up period of 50 months. Self-reported weight and physical activity levels had been validated previously. The adjusted mean difference in weight gain relative to never-smokers (the reference group) was estimated for different levels of tobacco exposure. RESULTS: After adjusting for age, baseline body mass index, sedentary lifestyle, changes in physical activity level, total energy intake, fiber intake, food consumption between meals, and sugary soft drink, fast food and alcohol consumption, it was found that individuals who stopped smoking during follow-up had a greater relative weight gain: men 1.63 kg (95% confidence interval [CI], 1.07-2.19 kg), and women 1.51 kg (95% CI, 1.11-1.91 kg). In addition, active smokers had a greater weight gain than never-smokers: men 0.49 kg (95% CI, 0.11-0.87 kg), and women 0.36 kg (95% CI, 0.07-0.65 kg). CONCLUSIONS: Individuals who stopped smoking during follow-up and active smokers both experienced significantly greater weight gains than never-smokers. This association between cardiovascular risk factors should be taken into account when developing prevention programs

Relationship between lactose digestion, gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption

Background: The relationship of symptoms with objective measurements, as well as some of the mechanisms involved in lactose tolerance after yoghurt consumption, remain unclear. Methods: The trial had a double-blind design in which 22 lactose malabsorbers received 25 g daily lactose in fresh (living bacteria > 108 cfu/g) yoghurt or heated (< 102 cfu/g) yoghurt for 15 days, followed by a crossover (15 days) after a wash-out period (14 days). The lactose digestion was determined by the breath H2 test, the gastric emptying (GE) with a 13C-acetate breath test and the revealed transit time (OCTT) by 15N-lactoseureide test. Subjects reported their gastrointestinal symptoms (GIS) in a validated questionnaire. Results: Breath H2 test indicated more effective lactose digestion after fresh yoghurt intake. The OCTT was shorter after heated yoghurt ingestion as compared with the fresh. There was lower severity of GIS (P < 0.05) after fresh yoghurt intake, and this showed an inverse correlation with OCTT (P < 0.05). Conclusions: Delayed orocoecal transit time was associated with fewer gastrointestinal symptoms. The improved lactose digestion and tolerance of fresh yoghurt should be mainly attributed to the presence of living bacteria

The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study; a multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control

Introduction: The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment. Objective: The study RESMENA-S aims to improve clinical criteria and biomarkers associated with MS though an integral therapy approach. Methods: The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice. Results: Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009). Conclusions: Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications