Virpi Lindi

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study

Objective:Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome.Design:Randomized controlled and individualized weight reduction intervention.Subjects:Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60±7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks.Measurements:Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction ⩾5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR.Results:In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S I and the change in body weight was found (r=−0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (−39±16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=−0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention.Conclusion:Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

Impact of the Pro12Ala polymorphism of the PPAR-γ2 gene on serum triacylglycerol response to n−3 fatty acid supplementation

Serum lipid responses to dietary modification are partly determined by genetic factors. The objective of the present study was to investigate the influence of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene on serum lipid and lipoprotein responses to n-3 fatty acid supplementation. A total of 76 men and 74 women (age 49+/-8 years, body mass index 26.5+/-3.0 kg/m(2)) participated in a controlled multi-center study. Subjects were randomly assigned to consume either fish oil supplements (3.6g n-3 fatty acids/day containing 2.4 g of EPA and DHA) or placebo capsules containing olive oil for 3 months. At baseline, the Pro12Ala polymorphism was not associated with serum total and lipoprotein lipid concentrations or lipoprotein lipase activity in the fasting state. After the 3-month study period, carriers of the Ala12 allele presented a greater decrease in serum triacylglycerol concentration in response to n-3 fatty acid supplementation than did subjects with the Pro12Pro genotype when the total dietary fat intake was below 37 E% (p=0.003) or the intake of saturated fatty acids was below 10 E% (p=0.006). Changes in serum total cholesterol, serum LDL cholesterol and HDL cholesterol concentrations were similar among the genotypes in the n-3 fatty acid supplementation group and in the placebo group. In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene may modify the inter-individual variability in serum triacylglycerol response to n-3 fatty acid supplementation.

Physical activity and sedentary behaviour in relation to cardiometabolic risk in children: cross-sectional findings from the Physical Activity and Nutrition in Children (PANIC) Study

BackgroundLower levels of physical activity (PA) and sedentary behaviour (SB) have been associated with increased cardiometabolic risk among children. However, little is known about the independent and combined associations of PA and SB as well as different types of these behaviours with cardiometabolic risk in children. We therefore investigated these relationships among children.MethodsThe subjects were a population sample of 468 children 6–8 years of age. PA and SB were assessed by a questionnaire administered by parents and validated by a monitor combining heart rate and accelerometry measurements. We assessed body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids and lipoproteins and blood pressure and calculated a cardiometabolic risk score using population-specific Z-scores and a formula waist circumference + insulin + glucose + triglycerides - HDL cholesterol + mean of systolic and diastolic blood pressure. We analysed data using multivariate linear regression models.ResultsTotal PA was inversely associated with the cardiometabolic risk score (β = -0.135, p = 0.004), body fat percentage (β = -0.155, p < 0.001), insulin (β = -0.099, p = 0.034), triglycerides (β = -0.166, p < 0.001), VLDL triglycerides (β = -0.230, p < 0.001), VLDL cholesterol (β = -0.168, p = 0.001), LDL cholesterol (β = -0.094, p = 0.046) and HDL triglycerides (β = -0.149, p = 0.004) and directly related to HDL cholesterol (β = 0.144, p = 0.002) adjusted for age and gender. Unstructured PA was inversely associated with the cardiometabolic risk score (β = -0.123, p = 0.010), body fat percentage (β = -0.099, p = 0.027), insulin (β = -0.108, p = 0.021), triglycerides (β = -0.144, p = 0.002), VLDL triglycerides (β = -0.233, p < 0.001) and VLDL cholesterol (β = -0.199, p < 0.001) and directly related to HDL cholesterol (β = 0.126, p = 0.008). Watching TV and videos was directly related to the cardiometabolic risk score (β = 0.135, p = 0.003), body fat percentage (β = 0.090, p = 0.039), waist circumference (β = 0.097, p = 0.033) and systolic blood pressure (β = 0.096, p = 0.039). Resting was directly associated with the cardiometabolic risk score (β = 0.092, p = 0.049), triglycerides (β = 0.131, p = 0.005), VLDL triglycerides (β = 0.134, p = 0.009), VLDL cholesterol (β = 0.147, p = 0.004) and LDL cholesterol (β = 0.105, p = 0.023). Other types of PA and SB had less consistent associations with cardiometabolic risk factors.ConclusionsThe results of our study emphasise increasing total and unstructured PA and decreasing watching TV and videos and other sedentary behaviours to reduce cardiometabolic risk among children.Trial registrationClinicalTrials.gov Identifier: NCT01803776.

Dietary factors associated with overweight and body adiposity in Finnish children aged 6-8 years: the PANIC Study.

Objectives:To investigate the associations of dietary factors with overweight, body fat percentage (BF%), waist circumference (WC) and hip circumference (HC) among children.Design:Cross-sectional analysis of the Physical Activity and Nutrition in Children (PANIC) Study among 510 children (263 boys, 247 girls) aged 6–8 years from Kuopio, Finland.Methods:The children’s weight, height, WC and HC were measured. Overweight was defined by International Obesity Task Force body mass index cutoffs. The BF% was measured by dual-energy X-ray absorptiometry, nutrient intakes and meal frequency by 4-day food records and eating behaviour by Children’s Eating Behaviour Questionnaire.Results:Daily consumption of all the three main meals was inversely associated with overweight (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.18–0.75), BF% (β −0.12, P=0.012), WC (β −0.16, P=0.002) and HC (β −0.15, P=0.002). Enjoyment of food, food responsiveness and emotional overeating were directly associated with overweight (OR 1.57, 95% CI 1.04–2.35; OR 4.68, 95% CI 2.90–7.54; OR 2.60, 95% CI 1.52–4.45, respectively), BF% (β 0.13, P=0.004; β 0.30, P<0.001; β 0.09, P=0.035, respectively), WC (β 0.14, P=0.003; β 0.40, P<0.001; β 0.19, P<0.001, respectively) and HC (β 0.15, P=0.001; β 0.38, P<0.001; β 0.15, P=0.001, respectively). Satiety responsiveness was inversely associated with overweight (OR 0.42, 95% CI 0.26–0.67), BF% (β −0.20, P<0.001), WC (β −0.26, P<0.001) and HC (β −0.26, P<0.001). Slowness in eating was inversely associated with overweight (OR 0.61, 95% CI 0.41–0.92), WC (β −0.16, P=0.001) and HC (β −0.17, P<0.001). Protein intake was directly associated with BF% (β 0.11, P=0.017), WC (β 0.11, P=0.020) and HC (β 0.13, P=0.008).Conclusions:Promoting regular consumption of main meals and healthy eating behaviours should be emphasized in the prevention of overweight among children. More research is needed on the association of protein-rich foods with body adiposity in children.

Associations of Motor and Cardiovascular Performance with Academic Skills in Children

PURPOSE We investigated the associations of cardiovascular and motor performance in grade 1 with academic skills in grades 1-3. METHODS The participants were 6- to 8-yr-old children with complete data in grades 1-2 for 174 children and in grade 3 for 167 children. Maximal workload during exercise test was used as a measure of cardiovascular performance. The shuttle run test (SRT) time, the errors in balance test, and the number of cubes moved in box and block test (BBT) were measures of motor performance. Academic skills were assessed using reading fluency, reading comprehension, and arithmetic skill tests. RESULTS Among boys, longer SRT time was associated with poorer reading fluency in grades 1-3 (β = -0.29 to -0.39, P < 0.01), reading comprehension in grades 1-2 (β = -0.25 to -0.29, P < 0.05), and arithmetic skills in grades 1-3 (β = -0.33 to -0.40, P < 0.003). Poorer balance was related to poorer reading comprehension (β = -0.20, P = 0.042). The smaller number of cubes moved in BBT was related to poorer reading fluency in grades 1-2 (β = 0.23-0.28, P < 0.03), reading comprehension in grade 3 (β = 0.23, P = 0.037), and arithmetic skills in grades 1-2 (β = 0.21-0.23, P < 0.043). Among girls, longer SRT time was related to poorer reading fluency in grade 3 (β = -0.27, P = 0.027) and arithmetic skills in grade 2 (β = -0.25, P = 0.040). The smaller number of cubes moved in BBT was associated with worse reading fluency in grade 2 (β = 0.26, P = 0.030). Cardiovascular performance was not related to academic skills. CONCLUSIONS Poorer motor performance was associated with worse academic skills in children, especially among boys. These findings emphasize early identification of children with poor motor performance and actions to improve these childrens motor performance and academic skills during the first school years.

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

Aims  Ghrelin is a gut–brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS).

Effect of a three-amino acid deletion in the alpha2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects.

BACKGROUND AND OBJECTIVE: The short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the α2B-adrenergic receptor gene was previously found to be associated with reduced basal metabolic rate in obese subjects. We investigated the effects of this polymorphism on changes in body weight in Finnish non-diabetic and type 2 diabetic subjects during a 10 y follow-up.DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10 y examinations.SUBJECTS: A total of 126 non-diabetic control subjects and 84 newly diagnosed, middle-aged type 2 diabetic patients from eastern Finland participated.MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and glycosylated hemoglobin A1c. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis.RESULTS: No significant differences were found in the prevalence of the 12Glu9 deletion polymorphism between non-diabetic and type 2 diabetic subjects. The non-diabetic subjects with the Glu9/Glu9 genotype had a greater increase in their mean body weight during 5 y follow-up than the non-diabetic subjects with other genotypes (changes in body weight 0.4±5.7, −0.5±6.4 and 3.4±4.9% for the Glu12/Glu12, Glu12/Glu9 and Glu9/Glu9 genotypes, respectively, P=0.040 for the difference between the groups). Also, the trend for the increment of body weight was statistically significant in the non-diabetic subjects with the Glu9/Glu9 genotype (P=0.012). The 12Glu9 polymorphism was not cross-sectionally or longitudinally associated with body weight in type 2 diabetic subjects.CONCLUSIONS: The genotype of two short alleles (Glu9/Glu9) was associated with an increase in body weight among non-diabetic subjects.

Dietary Intake, FTO genetic variants, and adiposity: A combined analysis of over 16,000 children and adolescents

The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.

Assessment of body composition by dual-energy X-ray absorptiometry, bioimpedance analysis and anthropometrics in children: the Physical Activity and Nutrition in Children study.

We compared InBody720 segmental multifrequency bioimpedance analysis (SMF‐BIA) with Lunar Prodigy Advance dual‐energy X‐ray absorptiometry (DXA) in assessment of body composition among 178 predominantly prepubertal children. Segmental agreement analysis of body compartments was carried out, and inter‐relationships of anthropometric and other measures of body composition were defined. Moreover, the relations of different reference criteria for excess body fat were evaluated.

Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study

We studied vitamin D intake, serum 25-hydroxyvitamin D (S-25(OH)D) concentration, determinants of S-25(OH)D and risk factors for S-25(OH)D <50 nmol/l in a population sample of Finnish children. We studied 184 girls and 190 boys aged 6-8 years, analysed S-25(OH)D by chemiluminescence immunoassay and assessed diet quality using 4-d food records and other lifestyle factors by questionnaires. We analysed the determinants of S-25(OH)D using linear regression and risk factors for S-25(OH)D <50 nmol/l using logistic regression. Mean dietary intake of vitamin D was 5·9 (sd 2·1) µg/d. Altogether, 40·8 % of children used no vitamin D supplements. Of all children, 82·4 % did not meet the recommended total vitamin D intake of 10 µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 48·7 % of daily intake. S-25(OH)D was <50 nmol/l in 19·5 % of children. Consumption of milk products was the main determinant of S-25(OH)D in all children (standardised regression coefficient β=0·262; P<0·001), girls (β=0·214; P=0·009) and boys (β=0·257; P=0·003) in multivariable models. Vitamin D intake from supplements (β=0·171; P=0·035) and age (β=-0·198; P=0·015) were associated with S-25(OH)D in girls. Children who drank ≥450 g/d of milk, spent ≥2·2 h/d in physical activity, had ≥13·1 h/d of daylight time or were examined in autumn had reduced risk for S-25(OH)D <50 nmol/l. Insufficient vitamin D intake was common among Finnish children, one-fifth of whom had S-25(OH)D <50 nmol/l. More attention should be paid to the sufficient intake of vitamin D from food and supplements, especially among children who do not use fortified milk products.