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PURPOSE: The interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization. METHODS: We genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake. RESULTS: We found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024). CONCLUSIONS: We have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.

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Obesity is a result of positive energy balance. The aim of this study was to measure (in crossover trials) the energy expenditure and oxidation of glucose and lipids, both at the fasting state and after an intake of meals with a varying macronutrient content, in normal-weight and overweight/obese people. In the study, 46 healthy adult males (23 with normal body weight and 23 overweight/obese), aged 21⁻58, were examined. During two consecutive visits, subjects received isocaloric standardized meals (450 kcal) with different content of basic nutrients. Resting metabolic rate and carbohydrate and fat utilization were evaluated during the fasting state and postprandially, using an indirect calorimetry method. Energy expenditure was higher in people with normal body weight and slightly higher after the high-carbohydrate meal. In overweight/obese people, increased expenditure was noted after normo-carbohydrate meal intake. The high-fat meal induced lower postprandial thermal response compared to a high-carbohydrate meal, both in people with normal body weight and in overweight/obese men. Glucose utilization was higher after the high-carbohydrate meal, and it was higher in the normal body weight group than in overweight/obese people. In addition, overweight/obese people showed a lower level of fatty acid oxidation under fasting conditions which, together with limited ability to oxidize energy substrates, depending on their availability, indicates that these people are characterized by lower metabolic flexibility.

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Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p < 0.02), but surprisingly lower daily food consumption (p < 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.

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BACKGROUND: BMI (body mass index) can be misleading regarding the level of adiposity in a normal-weight individual. Recently, a bioelectrical impedance analysis (BIA) method was developed that can measure body composition variables. The main objectives of this study were to use BIA to compare the body composition variables between chronic non-diabetic schizophrenic patients with normal weight and healthy individuals. The secondary objective was to compare the nutritional pattern of schizophrenia patients with that of matched healthy subjects, and to identify possible relationships between the content of different components of their diet and visceral adiposity. METHODS: The subjects were 52 normal-weight patients (33 males and 19 females) diagnosed with schizophrenia based on the DSM-IV and 45 (23 males and 22 females) BMI- matched controls. The patients had been receiving atypical or typical antipsychotic agents for at least one year before enrollment into the study but continuously for 3 months preceding the study and were psychiatrically stable. Body fat (kg), percent (%) body fat, fat-free mass, VAT (visceral adipose tissue) and SAT (subcutaneous adipose tissue) were measured using the bioelectrical impedance analysis (BIA) method. Daily food rations (DFR) were quantitatively evaluated by a 24-h dietary recall method covering 3 days preceding the examination. RESULTS: In normal-weight patients schizophrenia was significantly linked with higher VAT, VAT/SAT ratio and lower fat- free mass. Men had over 5 times and women over 2 times as much VAT as BMI matched groups. In women with schizophrenia and in their controls, the amount of magnesium, niacin and vitamin B6 in their diet inversely correlated with VAT, while in men lower zinc and vitamin C intake was related to higher visceral adiposity. CONCLUSIONS: Our study has shown that normal-weight patients with chronic schizophrenia have higher levels of visceral fat (VAT) than controls but similar volume of subcutaneous adipose tissue (SAT). Although no clear conclusion can be made regarding cause-and-effect relationships between the dietary content of food served to our patients and visceral obesity, we suggest that schizophrenia diet should be further investigated as a possible factor related to this type of obesity.

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