Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.
Cites: Cell. 1992 Mar 6;68(5):879-871312391
Cites: J Immunol. 2005 Mar 1;174(5):2981-915728511
Cites: Biochem J. 1992 Oct 1;287 ( Pt 1):237-401417777
High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation.
Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher's Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network.
We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals.
This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.
Cites: Ann Clin Res. 1973 Jun;5(3):109-414584134
Cites: Genome Biol. 2011;12(3):R2221410973
Cites: Nat Genet. 2006 Feb;38(2):218-2216429159
Cites: PLoS Genet. 2006 Aug 18;2(8):e13016934000
Cites: Am J Hum Genet. 2007 Jun;80(6):1024-3617503322
Cites: Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G1-417218471
Cites: Diabetologia. 2008 Jan;51(1):62-917972059
Cites: Bioinformatics. 2008 Mar 1;24(5):719-2018024473
Cites: Genome Res. 2008 May;18(5):706-1618347327
Cites: Am J Hum Genet. 2008 Aug;83(2):180-9218674750
The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known.
To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic and shared environmental effects by studying monozygotic intrapair differences.
Two cross-sectional samples of healthy adult monozygotic and dizygotic twins were drawn from population-based Danish and Finnish national twin registries (n = 996 and n = 309).
CRF was defined as VO2max divided by fat-free mass. Insulin sensitivity and acute insulin response indices were derived from an oral glucose tolerance test. A continuous metabolic syndrome score was calculated. Visceral and liver fat were measured in the Finnish sample. Associations were analyzed separately in both cohorts with multivariate linear regression and aggregated with meta-analytic methods.
Insulin sensitivity, acute insulin response, metabolic syndrome score, visceral, and liver fat amount had strong and statistically significant associations with FMI (
0.53 to 0.79), whereas their associations with CRF and FFMI were at most weak (
0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern.
Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants.
The study aimed to determine whether alcohol use during late adolescence contributes to the weight gain from adolescence to young adulthood or risk of obesity or waist circumference at young adulthood.
A population-based, longitudinal study of 5563 Finnish twins born in 1975-1979 and surveyed at ages 16 (T1), 17 (T2), 18 (T3) and 23-27 (T4) years. Drinking habits, height and weight were self-reported at T1, T2, T3 and T4; waist circumference was self-measured at T4. As potential confounders, we used smoking, diet, physical activity, place of residence, socio-economic status and parents' body mass index (BMI).
Compared to the reference group (drinking once to twice per month), the BMI increase from T3 to T4 was less among abstaining men (-0.62 kg/m(2), (95% CI -1.04, -0.20)) and among women in those drinking less than monthly (-0.38 kg/m(2), (-0.71, -0.04)). In women, at least weekly drinking was associated with larger waist circumference (Beta 1.55 cm, (0.48, 2.61)), but this became statistically non-significant after adjusting for potential confounders. In a multilevel model for change, drinking frequency was not associated with weight change in women; in men, a negative association was seen, but it was statistically non-significant after adjusting for potential confounders.
These results from a population-based study with a large set of confounding variables suggest that alcohol use during adolescence has at most a minor effect on weight gain or development of abdominal obesity from adolescence to young adulthood.
Cites: Scand J Med Sci Sports. 2002 Jun;12(3):179-8512135451
This study identified genetic and environmental influences on the tracking of body size from birth to 16 to 18.5 years of age.
Longitudinal information was collected from a nationally representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979) and their parents through questionnaires mailed when the twins were ages 16 and 18.5 years old. The sample included 702 monozygotic, 724 same-sex dizygotic, and 762 opposite-sex dizygotic sets of twins. The measures used were length, weight, ponderal index (kilograms per cubic meters), and gestational age at birth, and height, weight, and body mass index (kilograms per square meters) at 16 to 18.5 years of age. The changes in genetic and environmental influences on body size from birth to early adulthood were analyzed by quantitative genetic modeling.
The twins who had a higher weight or ponderal index at birth were taller and heavier in early adulthood, whereas those who were longer at birth were taller, but not heavier, later in life. Adult height was affected more by the birth size than body mass index. In the genetic modeling analyses, the genetic factors accounting for the variation of body size became more apparent with age, and both genetic and environmental influences on stature had a sizable carry-over effect from birth to late adolescence, whereas for relative weight, the influences were more age-specific.
The genetic and environmental architecture of body size changes from birth to adulthood. Even in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long-lasting effects of fetal environment on final body size.
The aim of this study was to investigate genetic and environmental influences on different aspects of physical activity in young adult twins.
We studied 1274 Finnish twins with a mean age of 22.4 yr, from the population-based FinnTwin12 study. Physical activity was assessed with the Baecke Questionnaire, yielding four indexes: the sport index, leisure time activity index, work index, and total score. Quantitative genetic analyses based on linear structural equations were used to estimate the contribution of genetic and environmental factors on these physical activity traits.
The overall heritability estimates were 64% (95% confidence interval (CI) = 0.56%-0.70%) for sports activity, 41% (95% CI = 0.31%-0.51%) for leisure time activity excluding sports, 56% (95% CI = 0.48%-0.63%) for physical activity at work, and 54% (95% CI = 0.45%-0.62%) for total physical activity. Unique environmental factors accounted for the rest of the trait variances. We did not find evidence for common environmental or dominant genetic influences. The heritability estimates did not differ between men and women, and no sex-specific genetic factors were found. Sports activity and leisure time activity excluding sports were associated (r = 0.27), and additive genetic factors explained 57% of their association.
Our results suggest that genetic factors contribute significantly to physical activity levels in young adults and that sports activity is under stronger genetic influence than leisure time physical activity excluding sports. We also concluded that physical activity at work does not seem to be associated with sports activities or other leisure time physical activity at this age.
Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P
The impact of diet on the gut microbiota has usually been assessed by subjecting people to the same controlled diet and thereafter following the shifts in the microbiota. In the present study, we used habitual dietary intake, clinical data, quantitative polymerase chain reaction, and denaturing gradient gel electrophoresis (DGGE) to characterize the stool microbiota of Finnish monozygotic twins. The effect of diet on the numbers of bacteria was described through a hierarchical linear mixed model that included the twin individuals, stratified by body mass index, and their families as random effects. The abundance and diversity of the bacterial groups studied did not differ between normal-weight, overweight, and obese individuals with the techniques used. Intakes of energy, monounsaturated fatty acids, n3 polyunsaturated fatty acids (PUFAs), n6 PUFAs, and soluble fiber had significant associations with the stool bacterial numbers (e.g., increased energy intake was associated with reduced numbers of Bacteroides spp.). In addition, co-twins with identical energy intake had more similar numbers and DGGE-profile diversities of Bacteroides spp. than did the co-twins with different intake. Moreover, the co-twins who ingested the same amounts of saturated fatty acids had very similar DGGE profiles of Bacteroides spp., whereas the co-twins with similar consumption of fiber had a very low bifidobacterial DGGE-profile similarity. In conclusion, our findings confirm that the diet plays an important role in the modulation of the stool microbiota, in particular Bacteroides spp. and bifidobacteria.
Obesity and the metabolic syndrome are established risk factors of venous thromboembolism. As most coagulation factors are produced exclusively by the liver and non-alcoholic fatty liver disease (NAFLD) is tightly related to metabolic disorders, we aimed at studying the association of liver fat with various coagulation factor activities.
Plasma prothrombin (PT) and activated partial thromboplastin time, activities of vWF:RCo, FVII, FVIII, FIX, FXI, FXII, FXIII, fibrinogen and D-dimer concentrations were measured in 54 subjects with and 44 without NAFLD diagnosed by proton magnetic resonance spectroscopy. Subjects were recruited retrospectively for metabolic studies in our laboratory. The body composition and features of insulin resistance were measured in all subjects.
To determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years.
Co-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests.
Sixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differences in eating behaviours.
The eating habits questionnaire revealed that physically active co-twins more frequently reported that it is easy to eat according to need, whereas overeating and/or restrictive eating was more common among the inactive co-twins (P = 0·035). Avoiding calories was more common among the active than inactive co-twins (P = 0·034). Based on food diaries the physically active co-twins had daily energy intake on average 15·5 kJ/kg higher than their inactive co-twins (P = 0·030). The active co-twins also had a higher intake of vitamin C (P = 0·004), total water (P = 0·044), legumes and nuts (P = 0·015) and sweets (P = 0·036), as well as a lower energy-adjusted intake of meat (P = 0·013).
The physically active persons seem to eat more but not necessarily healthier food. However, habitual physical activity may help in eating according to need and in reaching and maintaining a healthy body composition. Therefore, it is necessary to incorporate both dietary and physical activity advice into health counselling.