N-3 polyunsaturated fatty acids, body fat and inflammation.

BACKGROUND: Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have been suggested to lower the risk of obesity and inflammation. We aimed to investigate if, among humans, intake of n-3 PUFAs was associated with i) total body fat, ii) body fat distribution and iii) obesity-related inflammatory markers. METHODS: The study population consisted of 1,212 healthy individuals with information on habitual food intake from food frequency questionnaires, six different measures of body fat, and levels of six circulating inflammatory markers. Multiple linear regression analysis of intakes of PUFAs in relation to outcomes were performed and adjusted for potential confounders. RESULTS: Absolute n-3 PUFA intake, but not n-3/n-6, was inversely associated with the different measures of body fat. Among n-3 PUFA derivatives, only α-linolenic acid (ALA) was inversely associated with body fat measures. No significant interactions with the dietary macronutrient composition were observed. Pro-inflammatory cytokines were not associated with absolute PUFA intake, but the macrophage inflammatory protein-1α (MIP-1α) was associated with the n-3/n-6 ratio. CONCLUSION: In humans, intake of n-3 PUFAs, in particular ALA, is beneficially associated with body fatness. The favourable association is, however, not reflected in systemic levels of pro-inflammatory cytokines, nor is it influenced by macronutrients in the diet.

Genetics of dietary habits and obesity - a twin study.

Obesity has become a major health concern due to the increased risk of co-morbidities, resulting in decreased quality of life, stigmatization, reduced working ability and early death. This causes a great challenge for the health care systems and results in increased direct costs related to treatment of obesity and co-morbidities, as well as increased indirect costs related to reduced function and withdrawal from the labour market. Both between and within societies, large variation in the prevalence of overweight and obesity exists. This variation is caused by differences in environmental exposures as well as genetic differences between individuals, resulting in differentiated susceptibility to environmental exposures. The evidence for genetic influence on anthropometry has previously been established and has been estimated to be 60-70% based on twin studies. These inter-individual differences can, however, not explain the increase in obesity prevalence during the past 70 years. Environmental factors must therefore play an important role in the obesity epidemic. Habitual diet is one of many environmental factors that potentially contribute to the inter-individual differences in body fat mass, but only limited evidence for associations between habitual dietary intake and anthropometry exists. Differences in habitual dietary intake are also partly determined by differences in genes influencing smell and taste preferences. But, so far, only few studies have investigated genetic influences on dietary intake in adults and the interplay between diet, genes and obesity. The focus of the thesis was to investigate the genetic and environmental influence on habitual diet and obesity as well as the association between habitual diet and anthropometry. The thesis is based on structural equation modelling of twin data from the Danish Twin Registry with special focus on the GEMINAKAR twin study that was performed in 1997-2000. In this study, anthropometric traits of the twin pairs were measured and habitual dietary intake was assessed through a food frequency questionnaire (FFQ). When studying body fat mass in population-based studies, the phenotype used is often the body mass index (BMI). This measure does, however, not specify whether excess body mass is due to excess fat mass and how the body fat is distributed. Studying the genetic and environmental correlations between the anthropometry measures in the GEMINAKAR sample showed that the genetic correlations between BMI, fat mass index (FMI) and waist circumference were high in men and that the genetic correlations between BMI, FMI, waist and hip circumference were high in women. For all anthropometric phenotypes, significant residual genetic influence existed. Based on information about habitual diet from the FFQ the genetic influence on total energy intake, macronutrient intake, as well as intake of energy from 20 food groups, was estimated. The proportion of variation in dietary intake explained by variation in genes differed between the dietary traits under study but for the majority of dietary variables the genetic influence was 20-50%. Accordingly, both diet and anthropometry is influenced by genetic variation. In order to control for potential confounding by genetic variation and shared environment on the association between habitual diet and body fat, the monozygotic twin pairs were selected and the associations between intrapair differences in dietary intake and intrapair differences in anthropometry were studied. For the majority of dietary traits, no associations or only weak associations were found. The study showed, however, consistent positive associations between intake of sugar-sweetened soft drink and BMI, FMI and waist circumference in men. Gene-environment interaction models showed that while high physical activity is associated with a down-regulation of genes predisposing to obesity, such effects were not found for protein intake. In conclusion, the studies included in this thesis contribute to the relatively limited existing literature, with insight into genetic determinants of habitual dietary intake, pleiotropic influences on anthropometry, and the interplay between diet, genes and obesity.

Modification effects of physical activity and protein intake on heritability of body size and composition.

BACKGROUND: The development of obesity is still a poorly understood process that is dependent on both genetic and environmental factors. OBJECTIVE: The objective was to examine how physical activity and the proportion of energy as protein in the diet modify the genetic variation of body mass index (BMI), waist circumference, and percentage body fat. DESIGN: Twins from Denmark (756 complete pairs) and Finland (278 complete pairs) aged 18-67 and 21-24 y, respectively, participated. The proportion of energy as protein in the diet was estimated by using food-frequency questionnaires. The participants reported the frequency and intensity of their leisure time physical activity. Waist circumference and BMI were measured. Percentage body fat was assessed in Denmark by using a bioelectrical impedance method. The data were analyzed by using gene-environment interaction models for twin data with the Mx statistical package (Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA). RESULTS: High physical activity was associated with lower mean values, and a high proportion of protein in the diet was associated with higher mean BMI, waist circumference, and percentage body fat and a reduction in genetic and environmental variances. Genetic modification by physical activity was statistically significant for BMI (-0.18; 95% CI: -0.31, -0.05) and waist circumference (-0.14; 95% CI: -0.22, -0.05) in the merged data. A high proportion of protein in the diet reduced genetic and environmental variances in BMI and waist circumference in Danish men but not in women or in Finnish men. CONCLUSIONS: Our results suggest that, in physically active individuals, the genetic variation in weight is reduced, which possibly suggests that physical activity is able to modify the action of the genes responsible for predisposition to obesity, whereas the protein content of the diet has no appreciable effect.

Studies of twins indicate that genetics influence dietary intake.

Habitual dietary intake is a complex behavior that may have both biological and nonbiological bases. We estimated the contribution of genetic and environmental influences on dietary intake in a large population-based sample of healthy twins. Data originated from a cross-sectional study of 600 male and female healthy twin pairs with self-reported food consumption frequency using a validated questionnaire with 247 foods and recipes. Estimates of relative proportion of additive genetic, nonadditive genetic, shared environmental, and unshared environmental effects on various aspects of dietary intake were obtained by quantitative genetic modeling of twin data based on linear structural equations. The analyses demonstrated genetic influence on total energy, macronutrient energy, and dietary fiber intakes, the glycemic index and the glycemic load of the foods consumed, and the dietary energy density, with significant heritability estimates ranging from 0.25 (0.11-0.38) to 0.47 (0.31-0.60) in men and 0.32 (0.12-0.48) to 0.49 (0.35-0.61) in women. When analyzing dietary intake as the intake of energy from 20 food groups, the genetic and environmental influences differed among food groups and between gender. For some food groups (fruit for both genders, poultry and eggs for men), no genetic influence was found, whereas nonadditive genetic effects were demonstrated for other food groups (juices and eggs for women). A number of food groups had shared environmental influences (potatoes, vegetables, fruits, poultry, fish, margarine, and candy). These results provide evidence for both genetic and shared environmental effects on dietary intake. Although the remaining nonshared environmental effects include measurement errors, there appears to be considerable potential for individually modifiable effects.