Changes in BMI and physical activity from youth to adulthood distinguish normal-weight, metabolically obese adults from those who remain healthy.

Highlights: Adults with MONW have a lower BMI during youth until young adulthood, but higher BMI after this than adults with metabolically healthy normal weight. Adults with MONW have a greater decrease in physical activity from youth to adulthood than other adults. Healthy lifestyle is important in the prevention of metabolic disorders, particularly in individuals who are slim in childhood. Background: Individuals with metabolically obese normal-weight (MONW) have higher risk of cardiovascular events than those with obesity but a metabolically healthy status. Etiological factors leading to MONW are not well known. We hypothesized distinct trajectories of changes in BMI and physical activity may modify metabolic risk and distinguish individuals with MONW from those who remain healthy. Methods: We compared the mean levels of BMI and physical activity at eight time points (1980, 1983, 1986, 1989, 1992, 2001, 2007, 2011) between MONW and healthy normal-weight adults using linear mixed-model analysis. The analyses included 1180 participants of the Cardiovascular Risk in Young Finns study, a population-based study that represents six different age cohorts 3, 6, 9, 12, 15 and 18 years of age at baseline. Results: Individuals with adult MONW had significantly lower BMI in childhood and young adulthood, but their BMI increased more than in other adults after this age (p<0.001for interaction between time and MONW status). Physical activity decreased relatively more since youth in individuals with adult MONW (p<0.001). Conclusions: Relative leanness in youth and subsequent weight gain in young adulthood, and a gradual decrease in physical activity levels from youth to adulthood, predispose normal-weight individuals to metabolic impairments. The results highlight the importance of a healthy lifestyle in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.

Increase in adiposity from childhood to adulthood predicts a metabolically obese phenotype in normal-weight adults.

Normal weight is associated with a favorable cardiometabolic risk profile and low risk of type 2 diabetes and cardiovascular disease. However, some normal-weight individuals-the "metabolically obese normal weight" (MONW)-show a cardiometabolic risk profile similar to the obese. Previous studies have shown that older age, central body fat distribution, and unfavorable lifestyle increase the risk of MONW. However, the role of early-life factors in MONW remains unknown. We examined the associations of early-life factors with adult MONW in 1178 individuals from the Cardiovascular Risk in Young Finns study who were followed up from childhood to adulthood. The strongest early predictor for adult MONW was an increase in BMI from childhood to adulthood (p = 3.1 × 10-11); each 1 SD increase in BMI z-score from childhood to adulthood led to a 2.56-fold increase in the risk of adult MONW (CI 95% = 1.94-3.38). Other significant predictors of adult MONW were male sex (OR = 2.38, 95% = 1.63-3.47, p = 7.0 × 10-6), higher childhood LDL cholesterol (OR = 1.41 per 1 SD increase in LDL cholesterol, CI 95% = 1.14-1.73, p = 0.001), and lower HDL cholesterol (OR = 1.51 per 1 SD decrease in HDL cholesterol, CI 95% = 1.23-1.85, p = 5.4 × 10-5). Our results suggest that an increase in adiposity from childhood to adulthood is detrimental to cardiometabolic health, even among individuals remaining normal weight.

Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.

Plasma polyunsaturated fatty acids are directly associated with cognition in overweight children but not in normal weight children.

AIM: Polyunsaturated fatty acids are essential nutrients for the normal development of the brain. We investigated the associations between plasma polyunsaturated fatty acids and cognition in normal weight and overweight children. METHODS: The study recruited 386 normal weight children and 58 overweight children aged six to eight years and blood samples were drawn after a 12-hour fast. We assessed plasma polyunsaturated fatty acids using gas chromatography, cognition using Raven's Coloured Progressive Matrices, and overweight and obesity using the age-specific and sex-specific cut-offs from the International Obesity Task Force. The data were analysed by linear regression analyses adjusted for age and sex. RESULTS: Higher proportions of eicosapentaenoic acid in plasma triacylglycerols (ß = 0.311, p = 0.020, p = 0.029 for interaction) and docosahexaenoic acid in plasma triacylglycerols (ß = 0.281, p = 0.038, p = 0.049 for interaction) were both associated with higher Raven's scores in overweight children but not in normal weight children. Higher eicosapentaenoic acid to arachidonic acid ratios in triacylglycerols (ß = 0.317, p = 0.019) and phospholipids (ß = 0.273, p = 0.046) were directly associated with the Raven's score in overweight children but not in normal weight children. CONCLUSION: These findings suggest that increasing the consumption of fish and other sources of eicosapentaenoic acid and docosahexaenoic acid may improve cognition among overweight children.

Association of plasma fatty acid composition with plasma irisin levels in normal weight and overweight/obese children.

BACKGROUND: Irisin has been suggested to protect against overweight. There are no previous data on the association of plasma fatty acid (FA) composition with plasma irisin. OBJECTIVES: We studied the association of FA composition with plasma irisin in normal weight and overweight/obese children. METHODS: This cross-sectional study included pre-pubertal children (388 normal weight children and 55 overweight/obese children); 6-9 years of age, taking part in the Physical Activity and Nutrition in Children Study. After an overnight fast, we measured plasma FA composition by gas chromatography and plasma irisin levels by enzyme-linked immunosorbent assay. RESULTS: Higher proportion of total monounsaturated fatty acids in plasma cholesteryl esters (CEs) (ß = 0.139, P = 0.003) and phospholipids (PLs) (ß = 0.147, P = 0.002) and lower proportion of total polyunsaturated fatty acids in plasma CE (ß = -0.130, P = 0.006) and PL (ß = -0.165, P < 0.001) were associated with higher plasma irisin level in the whole study group. The association of plasma FA composition with plasma irisin level was stronger among overweight/obese children compared to normal weight children. Higher proportion of γ-linolenic acid (ß = 0.324, P = 0.017) and lower proportion of linoleic acid (ß = -0.397, P = 0.005) in plasma CE were related to higher plasma irisin level among overweight/obese children, indicating the direct association of estimated D6D activity in plasma CE (ß = 0.343, P = 0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma CE (ß = 0.345, P = 0.012) and PL (ß = 0.292, P = 0.033) and higher proportion of adrenic acid (ß = 0.366, P = 0.008) and docosapentaenoic acid (ß = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin level among overweight/obese children. CONCLUSION: Metabolically unfavourable plasma FA profile was associated with higher plasma irisin level especially in overweight/obese children, suggesting that excess body fat might modulate these relationships.

Associations of cardiorespiratory fitness, physical activity, and adiposity with arterial stiffness in children.

Associations of cardiorespiratory fitness (CRF), physical activity (PA), sedentary behavior, and body fat percentage (BF%) with arterial stiffness and dilation capacity were investigated in 160 prepubertal children (83 girls) 6-8 years of age. We assessed CRF (watts/lean mass) by maximal cycle ergometer exercise test, total PA, structured exercise, unstructured PA, commuting to and from school, recess PA and total and screen-based sedentary behavior by questionnaire, BF% using dual-energy X-ray absorptiometry, and arterial stiffness and dilation capacity using pulse contour analysis. Data were adjusted for sex and age. Poorer CRF (standardized regression coefficient ß = -0.297, P < 0.001), lower unstructured PA (ß = -0.162, P = 0.042), and higher BF% (ß = 0.176, P = 0.044) were related to higher arterial stiffness. When CRF, unstructured PA, and BF% were in the same model, only CRF was associated with arterial stiffness (ß = -0.246, P = 0.006). Poorer CRF was also related to lower arterial dilation capacity (ß = 0.316, P < 0.001). Children with low CRF (< median) and high BF% (≥ median; P = 0.002), low CRF and low unstructured PA (< median; P = 0.006) or children with low unstructured PA and high BF% (P = 0.005) had higher arterial stiffness than children in the opposite halves of these variables. Poor CRF was independently associated with increased arterial stiffness and impaired arterial dilation capacity among children.

Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study.

OBJECTIVES: PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase (ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. METHODS: Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. RESULTS: Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after 2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up (P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. CONCLUSION: PNPLA3 148M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children.