Leonie H. Bogl

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.

GLP-1 Responses Are Heritable and Blunted in Acquired Obesity With High Liver Fat and Insulin Resistance

OBJECTIVE Impaired incretin response represents an early and uniform defect in type 2 diabetes, but the contributions of genes and the environment are poorly characterized. RESEARCH DESIGN AND METHODS We studied 35 monozygotic (MZ) and 75 dizygotic (DZ) twin pairs (discordant and concordant for obesity) to determine the heritability of glucagon-like peptide 1 (GLP-1) responses to an oral glucose tolerance test (OGTT) and the influence of acquired obesity to GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) during OGTT or meal test. RESULTS The heritability of GLP-1 area under the curve was 67% (95% CI 45–80). Cotwins from weight-concordant MZ and DZ pairs and weight-discordant MZ pairs but concordant for liver fat content demonstrated similar glucose, insulin, and incretin profiles after the OGTT and meal tests. In contrast, higher insulin responses and blunted 60-min GLP-1 responses during the OGTT were observed in the heavier as compared with leaner MZ cotwins discordant for BMI, liver fat, and insulin sensitivity. Blunted GLP-1 response to OGTT was observed in heavier as compared with leaner DZ cotwins discordant for obesity and insulin sensitivity. CONCLUSIONS Whereas the GLP-1 response to the OGTT is heritable, an acquired unhealthy pattern of obesity characterized by liver fat accumulation and insulin resistance is closely related to impaired GLP-1 response in young adults.

Association of body mass index with arterial stiffness and blood pressure components: a twin study.

RATIONALE Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. METHODS We studied 228 monozygotic and 150 dizygotic twin pairs aged 18-82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m(2)). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. RESULTS Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = -0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%-77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15-0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). CONCLUSION Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important.

Abdominal obesity and circulating metabolites: A twin study approach.

OBJECTIVE To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. SUBJECTS AND METHODS Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference ≥3 kg/m(2)). RESULTS Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. CONCLUSIONS A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability.

Dietary omega-3 polyunsaturated fatty acid intake is related to a protective high-density lipoprotein subspecies profile independent of genetic effects: A monozygotic twin pair study

BACKGROUND Studies on diet and high-density lipoprotein (HDL) subspecies distribution are limited. OBJECTIVE We examined the relationship between macronutrient composition and lipoprotein particle size and HDL subspecies independent of genetic effects by studying monozygotic (MZ) twins. METHODS 24 healthy MZ twin pairs aged 23-33 years were identified from two longitudinal population-based studies, FinnTwin16 and FinnTwin12. Total energy and nutrient intake were assessed with 3-day food records and physical activity was measured by the Baecke index. HDL subspecies distribution was determined by non-denaturing gradient gel electrophoresis. Associations between diet composition and HDL mean particle size were determined by multivariate nutrient density models adjusted for confounding variables. RESULTS Substituting one energy percentage from omega-3 polyunsaturated fatty acids (n-3 PUFAs) for a corresponding amount of energy from other type of fats was related to changes in the relative proportions of the HDL subspecies 2b, 3a and 3b toward a larger mean particle size in men (β ± SE: 1.00 ± 0.26 nm, p = 0.004) and women (β ± SE: 0.90 ± 0.21 nm, p = 0.001). This association remained significant in analyses controlling for genetic and shared environmental influences using within-pair differences of the measures in MZ twin pairs (β ± SE: 0.37 ± 0.14 nm, p = 0.019). Twins with the higher n-3 PUFA intake had significantly higher proportions of large HDL(2b) particles and lower proportions of smaller-sized HDL(3a) and HDL(3b) particles as compared to their co-twins with lower intakes (p < 0.05). CONCLUSIONS Our data suggest that n-3 PUFA intake is associated with a favorable change in the distribution of HDL subspecies towards larger particles independent of genetic and shared environmental factors.

Dietary Patterns of European Children and Their Parents in Association with Family Food Environment: Results from the I.Family Study

The aim of this study was to determine whether an association exists between children’s and parental dietary patterns (DP), and whether the number of shared meals or soft drink availability during meals strengthens this association. In 2013/2014 the I.Family study cross-sectionally assessed the dietary intakes of families from eight European countries using 24-h dietary recalls. Usual energy and food intakes from six- to 16-year-old children and their parents were estimated based on the NCI Method. A total of 1662 child–mother and 789 child–father dyads were included; DP were derived using cluster analysis. We investigated the association between children’s and parental DP and whether the number of shared meals or soft drink availability moderated this association using mixed effects logistic regression models. Three DP comparable in children and parents were obtained: Sweet & Fat, Refined Cereals, and Animal Products. Children were more likely to be allocated to the Sweet & Fat DP when their fathers were allocated to the Sweet & Fat DP and when they shared at least one meal per day (OR 3.18; 95% CI 1.84; 5.47). Being allocated to the Sweet & Fat DP increased when the mother or the father was allocated to the Sweet & Fat DP and when soft drinks were available (OR 2.78; 95% CI 1.80; 4.28 or OR 4.26; 95% CI 2.16; 8.41, respectively). Availability of soft drinks and negative parental role modeling are important predictors of children’s dietary patterns.

Fat, sugar and water intakes among families from the IDEFICS intervention and control groups: first observations from I.Family.

The objective of this paper is to investigate differences in diets of families in intervention versus control communities 5 years after the Identification and Prevention of Dietary‐ and Lifestyle‐Induced Health Effects in Children and Infants intervention ended.

Improving the accuracy of self-reports on diet and physical exercise: the co-twin control method.

The objective was to examine the association between several obesity-related nongenetic behaviors and body mass index (BMI) and waist circumference (WC) in young adult twins using reports from both twins on their similarities and differences. A total of 713 monozygotic (MZ) and 698 same-sex dizygotic (DZ) twin pairs aged 22-28 years filled in structured questionnaires to compare their eating, physical activity and dieting behavior with their co-twins behavior, and to report their own eating and exercise habits. In both MZ and DZ pairs, the co-twins for whom both twin pair members concordantly answered that this twin eats more, snacks more, eats more fatty foods and sweet and fatty delicacies, chooses less healthy foods, eats faster and exercises less, had significantly higher BMIs (0.6-2.9 kg/m(2)) and WCs (1.5-7.5 cm). Multivariate regression analysis identified co-twin differences in the amount of food consumed as the strongest independent predictor of intrapair differences in BMI (beta = 0.63 and 1.21, for MZ and DZ, respectively, p < .001) and WC (beta = 1.52 and 3.53, for MZ and DZ, respectively, p < .001). Higher leisure-time physical activity and healthier dietary choices clustered in the same subjects. The measurement of habitual dietary intake and physical activity has previously relied on subjective self-reports that are prone to misreporting. By using comparative measures within twin pairs we found that the amount of food consumed is the major contributor to obesity independent of genetic predisposition.

Association between serum fatty acids and lipoprotein subclass profile in healthy young adults: Exploring common genetic and environmental factors

OBJECTIVE Little is known about the associations of serum fatty acids with lipoprotein profile and the underlying genetic and environmental etiology of these relationships. We aimed to analyze the phenotypic association of serum n-6 and n-3 polyunsaturated (PUFAs), monounsaturated (MUFAs) and saturated (SFAs) fatty acids (relative proportion to total fatty acids) with lipids and lipoproteins, and to quantify common genetic and environmental factors determining their covariation. METHODS Two cohorts of healthy Finnish twins were assessed in young adulthood. Data were available for 1269 individual twins including 561 complete pairs. Serum metabolites were measured by nuclear magnetic resonance spectroscopy. Bivariate quantitative genetic models were used to decompose the phenotypic covariance between the pairs of traits into genetic and environmental components. RESULTS Among the strongest correlations observed, serum total n-6 PUFAs and linoleic acid were inversely (max. r=-0.65) and MUFAs positively (max. r=0.63) correlated with triglycerides and very low-density lipoprotein (VLDL) particle concentration, particularly with large VLDL (for n-6 PUFAs) and medium VLDL (for MUFAs). Genetic factors significantly contributed to their covariance with bivariate heritability estimates ranging from 44% to 56% for n-6 PUFAs and 58% to 66% for MUFAs. Genetic correlations with lipid traits were moderate to high (max. rA=-0.59 and 0.70 for n-6 PUFAs and MUFAs, respectively). Statistically significant, but substantially weaker phenotypic correlations of total n-3 PUFAs, docosahexaenoic acid (DHA) and SFAs with lipoprotein profile were not decomposed into their genetic and environmental components. CONCLUSION Shared genetic factors are important in explaining why higher concentrations of serum n-6 PUFAs and lower concentrations of serum MUFAs strongly associate with lower triglyceride and VLDL particle concentrations.

Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity

Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain.