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Our understanding of the pathophysiology of obesity remains at best incomplete despite a century of research. During this time, two alternative perspectives have helped shape thinking about the etiology of the disorder. The currently prevailing view holds that excessive fat accumulation results because energy intake exceeds energy expenditure, with excessive food consumption being the primary cause of the imbalance. The other perspective attributes the initiating cause of obesity to intrinsic metabolic defects that shift fuel partitioning from pathways for mobilization and oxidation to those for synthesis and storage. The resulting reduction in fuel oxidation and trapping of energy in adipose tissue drives a compensatory increase in energy intake and, under some conditions, a decrease in expenditure. This theory of obesity pathogenesis has historically garnered relatively less attention despite its pedigree. Here, we present an updated comprehensive formulation of the fuel partitioning theory, focused on evidence gathered over the last 80 years from major animal models of obesity showing a redirection of fuel fluxes from oxidation to storage and accumulation of excess body fat with energy intake equal to or even less than that of lean animals. The aim is to inform current discussions about the etiology of obesity and by so doing, help lay new foundations for the design of more efficacious approaches to obesity research, treatment and prevention., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Obesity in humans represents a cumulative retention of a tiny fraction of total energy intake as fat, which is accompanied by growth of the metabolically active, energy-demanding, lean body mass. Since the energy balance regulation operates irrespective of the excess fat storage, availability of the required energy supplies is a permissive condition for obesity development. It occurs predominantly among people genetically predisposed and/or living with social or mental challenges. I propose a theory in which the body responds to social disruptions as threats of a future lack of food by an adiposity force building a reserve of energy independent of the regulation of the energy balance. It is based on the assumption that our evolutionary development required collaboration in gathering and sharing of food, combined with precautionary measures against anticipated failing food supplies. Social challenges are perceived as such threats, which activate the adiposity force through the brain to instigate the growth of fat and lean mass by neuro-hormonal signalling. If both perceived social threats and food abundance continue, the adiposity force pushes the fat accretion process to continue without inhibition by feedback signals from the fat mass, eventually leading to more obesity, and more so among the genetically predisposed. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Obesity is now a global pandemic, but there is little consensus about the causes.

Background: During the last decades, the prevalence of obesity [body mass index (BMI): weight/height2), ≥30.00 kg/m2] among adults has increased considerably. We examined whether this increase in a high-income, welfare state, like Denmark was driven by age, period or cohort effects, which would inform preventive strategies aiming at reducing the prevalence., Methods: We used data from the National Representative Health and Morbidity Studies, which are representative surveys of the Danish adult population (age 16 years and above), conducted in 1987, 1994, 2000, 2005, 2010, 2013, 2017 and 2021 (N = 91 684). Participants reported height and weight, from which BMI was calculated after correction for systematic bias in self-reported data and non-response. Age, survey year and birth cohorts were mutually adjusted and adjusted for sex in generalized linear models., Results: The obesity prevalence increased from 6.1% in 1987 to 18.4% in 2021, similarly in men (18.8%) and women (18.0%) and in all age groups. Age had an inverted u-shaped effect on the prevalence. Compared with individuals aged 16-24 years, the highest rate of obesity was seen for the age group 55-64 years [rate ratio 3.27, 95% confidence interval (CI): 2.58; 4.14]. The increasing rate for each recent survey year over time was compatible with a period effect without any birth cohort effects. The rate for obesity in 2021 was 4.16 in 1987 vs. 1987 (95% CI: 3.10; 5.59)., Conclusions: Obesity prevalence in Denmark increased steadily during the period 1987 through 2021, primarily driven by secular changes over time across all ages and birth cohorts., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits., Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment., Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10 -7 , with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P enrichment  = 1; childhood P enrichment  = 2.00 × 10 -4 ; adolescence P enrichment  = 2.10 × 10 -7 )., Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Aims/hypothesis: We aimed to investigate whether the impact of obesity and unfavourable lifestyle on type 2 diabetes risk is accentuated by genetic predisposition., Methods: We examined the joint association of genetic predisposition, obesity and unfavourable lifestyle with incident type 2 diabetes using a case-cohort study nested within the Diet, Cancer and Health cohort in Denmark. The study sample included 4729 individuals who developed type 2 diabetes during a median 14.7 years of follow-up, and a randomly selected cohort sample of 5402 individuals. Genetic predisposition was quantified using a genetic risk score (GRS) comprising 193 known type 2 diabetes-associated loci (excluding known BMI loci) and stratified into low (quintile 1), intermediate and high (quintile 5) genetic risk groups. Lifestyle was assessed by a lifestyle score composed of smoking, alcohol consumption, physical activity and diet. We used Prentice-weighted Cox proportional-hazards models to test the associations of the GRS, obesity and lifestyle score with incident type 2 diabetes, as well as the interactions of the GRS with obesity and unfavourable lifestyle in relation to incident type 2 diabetes., Results: Obesity (BMI ≥ 30 kg/m 2 ) and unfavourable lifestyle were associated with higher risk for incident type 2 diabetes regardless of genetic predisposition (p > 0.05 for GRS-obesity and GRS-lifestyle interaction). The effect of obesity on type 2 diabetes risk (HR 5.81 [95% CI 5.16, 6.55]) was high, whereas the effects of high genetic risk (HR 2.00 [95% CI 1.76, 2.27]) and unfavourable lifestyle (HR 1.18 [95% CI 1.06, 1.30]) were relatively modest. Even among individuals with low GRS and favourable lifestyle, obesity was associated with a >8-fold risk of type 2 diabetes compared with normal-weight individuals in the same GRS and lifestyle stratum., Conclusions/interpretation: Having normal body weight is crucial in the prevention of type 2 diabetes, regardless of genetic predisposition.

Objectives: Transportation noise has been associated with markers of obesity. We aimed to investigate whether road traffic and railway noise were associated with weight gain during and after pregnancy., Methods: Among the women participating in the Danish National Birth Cohort, 74 065 reported on weight before and during the pregnancy (gestational week 30) and 52 661 reported on weight before and 18 months after pregnancy. Residential address history from conception to 18 months after pregnancy was obtained in national registers, and road traffic and railway noise were modelled for all addresses. Associations between noise and gestational weight gain (GWG) and postpartum weight retention (PPWR) were analysed using the linear and log-binomial regression., Results: A 10 dB(A) higher road traffic noise was associated with an increase in GWG of 3.8 g/week (95% CI 2.3 to 5.3) and PPWR of 0.09 kg (95% CI 0.02 to 0.16). For PPWR, this association seemed confined to women who were overweight (0.17 kg, 95% CI 0.02 to 0.32) or obese (0.49 kg, 95% CI 0.26 to 0.73) before pregnancy. Further adjustment by nitrogen dioxide reduced GWG risk estimates and slightly increased PPWR risk estimates. Railway noise ≥65 dB(A) was associated with an increase in GWG of 4.5 g/week (95% CI -2.7 to 11.6) and PPWR of 0.26 kg (95% CI -0.09 to 0.60) compared with levels <55 dB(A)., Conclusions: Our findings suggest that road traffic noise is associated with weight gain during and after the pregnancy, which adds to the literature linking transportation noise to adiposity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Obesity has inconsistent associations with broad personality domains, possibly because the links pertain to only some facets of these domains. Collating published and unpublished studies (N = 14 848), we meta-analysed the associations between body mass index (BMI) and Five-Factor Model personality domains as well as 30 Five-Factor Model personality facets. At the domain level, BMI had a positive association with Neuroticism and a negative association with Conscientiousness domains. At the facet level, we found associations between BMI and 15 facets from all five personality domains, with only some Neuroticism and Conscientiousness facets among them. Certain personality-BMI associations were moderated by sample properties, such as proportions of women or participants with obesity; these moderation effects were replicated in the individual-level analysis. Finally, facet-based personality "risk" scores accounted for 2.3% of variance in BMI in a separate sample of individuals (N = 3569), 409% more than domain-based scores. Taken together, personality-BMI associations are facet specific, and delineating them may help to explain obesity-related behaviours and inform intervention designs. Preprint and data are available at https://psyarxiv.com/z35vn/., (© 2019 World Obesity Federation.)

Background Childhood weight trajectories may influence cardiometabolic traits and thereby the risk of venous thromboembolism ( VTE ) later in life. We examined whether overweight and changes in weight status during childhood were associated with risk of VTE in adulthood. Methods and Results We used Danish medical registries to conduct a population-based cohort study of Danish schoolchildren aged 7 to 13 years and born during 1930-1989. We calculated body-mass index ( BMI ) z-scores based on weight and height measurements. We estimated hazard ratios using Cox regressions to examine associations between changes in BMI z-scores from 7 to 13 years of age and the subsequent risk of VTE . Among 313 998 children, 5007 girls and 5397 boys were diagnosed with VTE as adults. Compared with children with a normal BMI (25th to 75th percentile category) at both ages, children with a BMI persistently above the 75th percentile had a 1.30- to 1.50-fold increased risk of VTE in adulthood. Children who experienced a BMI increase from the 25th to 75th or >75th to 90th percentile to a higher percentile category had a 1.35- to 1.70-fold increased risk of adulthood VTE . Children whose BMI percentile category decreased between 7 and 13 years of age had a VTE risk similar to that of children with a persistently normal BMI . Conclusions Risk of VTE in adulthood was higher in children with a persistently above-average BMI . Whereas weight gain from 7 to 13 years of age additionally increased VTE risk, remission from overweight by 13 years of age completely reverted the risk.

Background/objectives: We investigated whether fat mass (FM) and total adipose tissue (TAT) can be used interchangeably and FM per TAT adds to metabolic risk assessment., Subjects/methods: Cross-sectional data were assessed in 377 adults (aged 18-60 years; 51.2% women). FM was measured by either 4-compartment (4C) model or quantitative magnetic resonance (QMR); total-, subcutaneous- and visceral adipose tissue (TAT, SAT, VAT), and liver fat by whole-body MRI; leptin, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein (CRP), and triglycerides; resting energy expenditure and respiratory quotient by indirect calorimetry were determined. Correlations and stepwise multivariate regression analyses were performed., Results: FM 4C and FM QMR were associated with TAT (r 4C  = 0.96, r QMR  = 0.99) with a mean FM per TAT of 0.85 and 1.01, respectively. Regardless of adiposity, there was a considerable inter-individual variance of FM/TAT-ratio (FM 4C /TAT-ratio: 0.77-0.94; FM QMR /TAT-ratio: 0.89-1.10). Both, FM 4C and TAT were associated with metabolic risks. Further, FM 4C /TAT-ratio was positively related to leptin but inversely with CRP. There was no association between FM 4C /TAT-ratio and VAT/SAT or liver fat. FM 4C /TAT-ratio added to the variance of leptin and CRP., Conclusions: Independent of FM or TAT, FM 4C /TAT-ratio adds to metabolic risk assessment. Therefore, the interchangeable use of FM and TAT to assess metabolic risks is questionable as both parameters may complement each other.

Background: The increasing incidence of inflammatory bowel disease (IBD) in western countries has led to the hypothesis that obesity-related inflammation could play a role in the etiology of IBD. However, this hypothesis lacks confirmation in studies of individuals prior to the typical onset of IBD in young adulthood., Methods: In a cohort of 316,799 individuals from the Copenhagen School Health Records Register (CSHRR), we examined whether BMI at ages 7 through 13 years was associated with later IBD. Linking the CSHRR to the Danish National Patient Register, we identified cases of Crohn's disease (CD) and ulcerative colitis (UC) diagnosed during follow-up. Cox regression was used to estimate the hazard ratios (HR) with 95% confidence intervals., Results: During 10 million person-years of follow-up, 1500 individuals were diagnosed with CD and 2732 with UC. At all examined ages, a 1 unit increase in BMI z-score was associated with a significantly decreased risk of UC (HRs = 0.9) and with a significantly increased risk of CD when diagnosed before age 30 (HRs = 1.2). We observed no associations between changes in BMI z-score between 7 and 13 years and later risk of CD or UC., Conclusion: We found a direct association between childhood BMI and CD diagnosed before 30 years of age, and an inverse association between childhood BMI and UC irrespective of age. Our results support the previous hypotheses of obesity being a risk factor for CD, and suggest that childhood underweight might be a risk factor for UC.

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology., (© The Author 2017. Published by Oxford University Press.)

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided., (© 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Seasonal variation in birth weight was found in a previous Danish study. In the present study we investigated if the seasonality in birth weight tracked into BMI at 7years of age, but found no seasonality of birth in either BMI, overweight, or obesity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective:  To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials., Design:  Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials., Data Sources:  Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015., Eligibility Criteria for Study Selection:  Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity., Results:  We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category., Conclusions:  We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions., Systematic Review Registration:  PROSPERO CRD42015015969., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Forty-nine known single nucleotide polymorphisms (SNPs) associating with body mass index (BMI)-adjusted waist-hip-ratio (WHR) (WHRadjBMI) were recently suggested to cluster into three groups with different associations to cardiometabolic traits. Genetic risk scores of the clusters on the risk of incident diabetes and associations with detailed cardiometabolic phenotypes were tested., Methods: In a prospective study of 6,121 Inter99 individuals, the risk of incident diabetes using Cox proportional hazards regression was evaluated. Using linear regession, the associations between genetic risk scores and anthropometry and blood samples at fasting and during an oral glucose tolerance test were tested. Analyses were adjusted for age, sex, and BMI., Results: Cluster 1 associated with an increased risk of diabetes (HR = 1.05, P = 2.74 × 10(-) (4) ) and with a poor metabolic profile, including fasting serum triglyceride (β = 0.98% mmol/L, P = 3.33 × 10(-) (8) ) and Matsuda index (β = -0.74%, P = 1.29 × 10(-) (4) ). No similar associations for Clusters 2 and 3 were found. The three clusters showed different patterns of association with waist circumference, hip circumference, and height., Conclusions: Our results suggest that the 49 WHRadjBMI-associated SNPs affect metabolic health differently depending on the cluster of SNPs. The clusters further associate differently with anthropometric measures., (© 2016 The Obesity Society.)

Objective: To examine how pre-pregnancy body mass index (BMI), parity, and pregnancy-related weight changes are associated with long-term risk of degenerative musculoskeletal conditions., Methods: A total of 79,687 mothers with singleton births from the Danish National Birth Cohort were included. Information on height and weight prior to pregnancy and 6 months postpartum as well as gestational weight gain (GWG) was obtained from telephone interviews, while parity was derived from the Danish Medical Birth Registry. Diagnoses of musculoskeletal conditions, including osteoarthritis, disc disorders, low back pain, and soft tissue disorders, were obtained from the Danish National Patient Registry. Hazard ratios (HRs) were estimated using a Cox proportional hazards regression model., Results: The cumulative incidence of musculoskeletal conditions during a median follow-up of 12.4 years was 19.7%. The risk of musculoskeletal conditions increased with both increasing pre-pregnancy BMI and increasing parity. Compared to normal-weight first-time mothers, the highest risk was seen in obese women with >2 births (HR 1.61 [95% confidence interval 1.41-1.83]). GWG of 10-15 kg was associated with the lowest risk of musculoskeletal conditions. Compared to women with no change in weight from preconception to 6 months after childbirth (±1 BMI unit), increasing postpartum weight increased the risk of musculoskeletal conditions in normal-weight and overweight women., Conclusion: Our findings indicate that high pre-pregnancy BMI increases the risk of degenerative musculoskeletal conditions. Low and high GWG, higher postpartum weight retention, and especially higher parity are associated with an increased risk. Prevention of being overweight before, during, and after pregnancy may reduce the risk of development of degenerative musculoskeletal conditions among mothers., (© 2016, American College of Rheumatology.)

Importance: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain., Objective: To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight., Design, Setting, and Participants: Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included., Exposures: Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level., Main Outcome and Measure: Offspring birth weight from 18 studies., Results: Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1×10(-5)), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions., Conclusions and Relevance: In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.

The aim was to study how, and to what degree, health-related quality of life (HRQOL), as assessed by children and their mothers, was related to overweight and obesity among children aged seven to nine years. Mother-child pairs of 149 non-overweight, 95 overweight and 16 obese children participated. We assessed HRQOL by the children's self-report and parent proxy report module of the PedsQL™ 4.0 Generic Core Scales. We found that non-overweight children scored HRQOL slightly higher than overweight ones but significantly higher than did obese children. The same pattern was seen for the mothers' proxy HRQOL score and mothers in general scored higher than the children did. The results indicate that mothers in general were not sufficiently aware of how overweight and obesity affect their children's HRQOL. The psychosocial dimension of HRQOL was the most important aspect for the children. Thus, there is a need for information of mothers/parents about the impact of overweight and obesity on children's HRQOL. Such intervention by health professionals may among other interventions help to prevent and reduce overweight and obesity among children and thus help to increase the children's HRQOL throughout their lives., (© The Author(s) 2014.)

Background: Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG), and whether this relationship depends on genetic makeup., Objective: To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity., Design: A nested case-cohort study based on the Danish National Birth Cohort (DNBC) sampling the most obese women (n = 990) and a random sample of the remaining participants (n = 1,128). Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4,841). We included 32 body mass index (BMI) associated single nucleotide polymorphisms (SNPs) and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS). Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined., Results: In the DNBC, each portion/week (150 g) of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01). For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01) per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings., Conclusion: We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs.

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Association studies have identified a number of loci that contribute to an increased body mass index (BMI), the strongest of which is in the first intron of the FTO gene on human chromosome 16q12.2. However, this region is both non-coding and under strong linkage disequilibrium, making it recalcitrant to functional interpretation. Furthermore, the FTO gene is located within a complex cis-regulatory landscape defined by a topologically associated domain that includes the IRXB gene cluster, a trio of developmental regulators. Consequently, at least three genes in this interval have been implicated in the aetiology of obesity., Methods: Here, we sequence a 2 Mb region encompassing the FTO, RPGRIP1L and IRXB cluster genes in 284 individuals from a well-characterised study group of Danish men containing extremely overweight young adults and controls. We further replicate our findings both in an expanded male cohort and an independent female study group. Finally, we compare our variant data with a previous study describing IRX3 and FTO interactions in this region., Results: We obtain deep coverage across the entire region, allowing accurate and unequivocal determination of almost every single nucleotide polymorphism and short insertion/deletion. As well as confirming previous findings across the interval, we identify a further novel age-dependent association upstream of IRX5 that imposes a similar burden on BMI to the FTO locus., Conclusions: Our findings are consistent with the hypothesis that chromatin architectures play a role in regulating gene expression levels across topological domains while our targeted sequence approach represents a widely applicable methodology for high-resolution analysis of regional variation across candidate genomic loci.

Background: Previous studies have shown an association between prepregnancy BMI and postpartum depression, but little is known about this association beyond one year postpartum and the influence of postpartum weight retention (PPWR)., Methods: We used data from 70355 mothers from the Danish National Birth Cohort to estimate the associations between maternal prepregnancy BMI and PPWR, respectively, and incident depression/anxiety disorders until six years postpartum. Outcome was depression or anxiety diagnosed clinically or filling a prescription for an antidepressant. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at the day of delivery. For the analysis regarding PPWR, follow-up started six months postpartum., Results: Underweight, overweight and obesity were associated with depression and/or anxiety disorders when compared to normal-weight, though the associations were attenuated after adjustments (HR 1.24 [95% CI 1.06-1.45], 1.05 [95% CI 0.96-1.15] and 1.07 [95% CI 0.95-1.21] for underweight, overweight and obese, respectively). Compared to mothers who had returned to their prepregnancy BMI, risk of depression/anxiety disorders was increased for mothers, who from prepregnancy to 6 months postpartum experienced either weight loss >1 BMI unit (HR 1.19 [95% CI 1.06-1.25]), weight gain of 2-3 BMI units (HR 1.23 [95% CI 1.08-1.40]), or weight gain of ≥3 BMI units (HR 1.21 [95% CI 1.05-1.40])., Limitation: Causal direction and mechanisms behind the associations are largely unknown., Conclusions: Low prepregnancy body weight and postpartum weight gain or loss are associated with occurrence of depression and anxiety disorders., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Studies suggest that gestational weight gain (GWG) and breastfeeding behavior may influence long-term maternal abdominal fat mass. However, this could be confounded by abdominal fat mass before pregnancy because it is unknown whether abdominal fat mass, independently of body size, affects GWG and breastfeeding behavior., Objective: We investigated how maternal prepregnancy fat distribution, described by waist circumference (WC) and body mass index (BMI), is associated with GWG and breastfeeding behavior., Design: We analyzed 1371 live births to 1024 women after enrollment in the Coronary Artery Risk Development in Young Adults study (1985-1996). For each birth, maternal prepregnancy BMI and WC were measured at year 0 (baseline), 2, 5, or 7 examinations. Recalled GWG and breastfeeding behavior were collected at years 7 and 10. GWG was analyzed by using linear regression and breastfeeding behavior by using logistic regression and discrete-time logistic regression., Results: Adjusted for potential confounders, a 1-cm larger WC adjusted for BMI was associated with a 0.19-kg (95% CI: -0.29-, -0.10-kg) lower GWG. In contrast, a 1-unit higher BMI adjusted for WC was associated with a 0.27-kg (95% CI: 0.06-, 0.47-kg) higher GWG. The OR for ever breastfeeding compared with never breastfeeding was 0.93 (95% CI: 0.90, 0.97) per 1-cm larger WC after adjustment for BMI, whereas it was 1.10 (95% CI: 1.02, 1.19) per 1-unit higher BMI adjusted for WC., Conclusions: Maternal prepregnancy body size was differently associated with GWG and breastfeeding behavior depending on the location of the fat mass. Thus, maternal fat distribution may be a more important determinant of GWG and breastfeeding behavior than BMI alone., (© 2015 American Society for Nutrition.)

Objective: To investigate the association between the intake of n-6 PUFA and subsequent change in body weight and waist circumference at different levels of the carbohydrate:protein ratio., Design: Follow-up study with anthropometric measurements at recruitment and on average 5·3 years later. Dietary intake was determined at recruitment by using an FFQ that was designed for the study and validated. We applied linear regression models with 5-year change in weight or waist circumference as outcome and including a two-way interaction term between n-6 PUFA and carbohydrate intakes, lower-order terms, protein intake, long-chain n-3 PUFA intake and other potential confounders. Due to adjustment for intake of protein, levels of carbohydrate indirectly reflect levels of the carbohydrate:protein ratio., Setting: Diet, Cancer and Health follow-up study, Denmark., Subjects: Women and men (n 29 152) aged 55 years., Results: For a high intake of n-6 PUFA (6·9 % of energy) v. a low intake of n-6 PUFA (3·4 % of energy), the difference in 5-year weight change was -189·7 g (95 % CI -636·8, 257·4 g) at a low carbohydrate:protein ratio and -86·7 g (95 % CI -502·9, 329·6 g) at a high carbohydrate:protein ratio; the differences in 5-year waist circumference change were 0·26 cm (95 % CI -0·47, 0·98 cm) and -0·52 cm (95 % CI -1·19, 0·15 cm), respectively. Inclusion of the dietary glycaemic index did not change the results., Conclusions: No consistent associations between the intake of n-6 PUFA and change in body weight or waist circumference at different levels of the carbohydrate:protein ratio were observed.

Objective: We studied the influence of maternal behavior on weight change from prepregnancy to 7 years postpartum., Methods: We used linear regression to study the independent and combined associations between self-reported behavior in pregnancy (dietary intake, leisure-time exercise, sedentary activity, smoking) and postpartum (breastfeeding duration and smoking) on weights at 6 months, 18 months, and 7 years postpartum., Results: Women's average 7-year weight gain was 2.07 kg, with 23% gaining >5 kg. Multivariable analyses suggested that women with healthier dietary intake, more leisure-time exercise, less sedentary behavior, and longer duration of breastfeeding on average gained 1.66 kg [95% confidence interval (CI): 1.40; 1.91] with a significantly reduced odds [OR 0.56 (95% CI: 0.49; 0.64)] of gaining >5 kg from prepregnancy to 7 years postpartum compared to women with none or one of these behaviors [mean gain 3.03 kg (95% CI: 2.68; 3.39)]. Women who ceased smoking had higher long-term weight gain than nonsmokers, but not smokers., Conclusions: Adherence to healthy behaviors during pregnancy lowered long-term weight gain considerably by lowering postpartum weight retention and subsequent weight gain. Public health efforts to help mothers achieve healthy behaviors might prevent childbearing-related weight gain., (© 2015 The Obesity Society.)

Objectives: Maternal body mass index (BMI), birth weight, and preschool BMI may help identify children at high risk of overweight as they are (1) similarly linked to adolescent overweight at different stages of the obesity epidemic, (2) linked to adult obesity and metabolic alterations, and (3) easily obtainable in health examinations in young children. The aim was to develop early childhood prediction models of adolescent overweight, adult overweight, and adult obesity., Methods: Prediction models at various ages in the Northern Finland Birth Cohort born in 1966 (NFBC1966) were developed. Internal validation was tested using a bootstrap design, and external validation was tested for the model predicting adolescent overweight using the Northern Finland Birth Cohort born in 1986 (NFBC1986)., Results: A prediction model developed in the NFBC1966 to predict adolescent overweight, applied to the NFBC1986, and aimed at labelling 10% as "at risk" on the basis of anthropometric information collected until 5 years of age showed that half of those at risk in fact did become overweight. This group constituted one-third of all who became overweight., Conclusions: Our prediction model identified a subgroup of children at very high risk of becoming overweight, which may be valuable in public health settings dealing with obesity prevention., (© 2014 The Obesity Society.)

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The intergenerational resemblance in body mass index may have increased during the development of the obesity epidemic due to changes in environment and/or expression of genetic predisposition., Objectives: This study investigates trends in intergenerational correlations of childhood body mass index (BMI; kg/m2) during the emergence of the obesity epidemic., Methods: The study population was derived from the Copenhagen School Health Records Register, which includes height and weight measurements since birth year 1930. Mothers and fathers with BMIs available at ages 7 (n = 25,923 and n = 20,972) or 13 years (n = 26,750 and n = 21,397), respectively, were linked through the civil registration system introduced in 1968 to their children with BMIs available at age 7 years. Age- and sex-specific BMI z-scores were calculated. Correlations were estimated across eight intervals of child birth years (1952-1989) separately by sex. Trends in these correlations were examined. Whereas the mother-child correlations reflected the biological relationship, a likely decline in the assignment of non-biological fathers through the registration system across time must be considered when interpreting the father-child correlations., Results: The BMI correlations between mothers and sons ranged from 0.29-0.36 and they decreased marginally, albeit significantly across time at ages 7-7 years (-0.002/year, p = 0.006), whereas those at 13-7 years remained stable (<0.0004/year, p = 0.96). Mother-daughter correlations ranged from 0.30-0.34, and they were stable at ages 7-7 years (0.0001/year, p = 0.84) and at 13-7 years (0.0004/year, p = 0.56). In contrast, father-son correlations increased significantly during this period, both at ages 7-7 (0.002/year, p = 0.007) and at ages 13-7 years (0.003/year, p<0.001), whereas the increase in father-daughter correlations were insignificant both at ages 7-7 (0.001/year, p = 0.37) and at ages 13-7 years (0.001/year, p = 0.18)., Conclusion: During the obesity epidemics development, the intergenerational resemblance with mothers remained stable, whereas the father-child BMI resemblance increased, possibly reflecting changes in family relationships, and unlikely to have influenced the epidemic.

A new report provides compelling evidence of the high prevalence of overweight and obesity throughout the world. The prevalence has increased since 1980, but at different rates across ages, times and locations. Studies exploring the causes of these differences could aid development of effective prevention strategies.

Background: Perinatal stress may programme overweight and obesity. We examined whether maternal pre- and post-natal bereavement was associated with overweight and obesity in young men., Methods: A cohort study was conducted including 119,908 men born from 1976 to 1993 and examined for military service between 2006 and 2011. Among them, 4,813 conscripts were born to mothers bereaved by death of a close relative from 12 months preconception to birth of the child (exposed group). Median body mass index (BMI) and prevalence of overweight and obesity were estimated. Odds ratio of overweight (BMI≥25 kg/m2) and obesity (BMI≥30 kg/m2) were estimated by logistic regression analysis adjusted for maternal educational level., Results: Median BMI was similar in the exposed and the unexposed group but the prevalence of overweight (33.3% versus 30.4%, p = 0.02) and obesity (9.8% versus 8.5%, p = 0.06) was higher in the exposed group. Conscripts exposed 6 to 0 months before conception and during pregnancy had a higher risk of overweight (odds ratio 1.15, 95% confidence interval (CI): 1.03; 1.27 and odds ratio 1.13, 95% CI: 1.03; 1.25, respectively). Conscripts born to mothers who experienced death of the child's biological father before child birth had a two-fold risk of obesity (odds ratio 2.00, 95% CI: 0.93; 4.31). There was no elevated risk in those who experienced maternal bereavement postnatally., Conclusion: Maternal bereavement during the prenatal period was associated with increased risk of overweight or obesity in a group of young male conscripts, and this may possibly be reflected to severe stress exposure early in life. However, not all associations were clear, and further studies are warranted.

Background: Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity. Hence, we examined whether dietary ascorbic acid, possibly in interaction with the genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHR), associates with subsequent annual changes in weight (∆BW) and waist circumference (∆WC)., Methods: A total of 7,569 participants' from MONICA, the Diet Cancer and Health study and the INTER99 study were included in the study. We combined 50 obesity associated single nucleotide polymorphisms (SNPs) in four genetic scores: a score of all SNPs and a score for each of the traits (BMI, WC and WHR) with which the SNPs associate. Linear regression was used to examine the association between ascorbic acid intake and ΔBW or ΔWC. SNP-score × ascorbic acid interactions were examined by adding product terms to the models., Results: We found no significant associations between dietary ascorbic acid and ∆BW or ∆WC. Regarding SNP-score × ascorbic acid interactions, each additional risk allele of the 14 WHR associated SNPs associated with a ∆WC of 0.039 cm/year (P = 0.02, 95% CI: 0.005 to 0.073) per 100 mg/day higher ascorbic acid intake. However, the association to ∆WC only remained borderline significant after adjustment for ∆BW., Conclusion: In general, our study does not support an association between dietary ascorbic acid and ∆BW or ∆WC, but a diet with a high content of ascorbic acid may be weakly associated to higher WC gain among people who are genetically predisposed to a high WHR. However, given the quite limited association any public health relevance is questionable.

Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal studies of obesity's causes and therapies distract attention from preventive efforts. Drawing on both empirical data and moral reasoning, we argue that the relevant attributions of responsibility and claims about distraction are not plausible, and that, therefore, there is no reason to single out the use of animals in obesity research as especially problematic.

Background: Pre- and perinatal factors and preschool body size may help identify children developing overweight, but these factors might have changed during the development of the obesity epidemic., Objective: We aimed to assess the associations between early life risk indicators and overweight at the age of 9 and 15 years at different stages of the obesity epidemic., Methods: We used two population-based Northern Finland Birth Cohorts including 4111 children born in 1966 (NFBC1966) and 5414 children born in 1985-1986 (NFBC1986). In both cohorts, we used the same a priori defined prenatal factors, maternal body mass index (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI (age 2-5 years). We used internal references in early childhood to define percentiles of body size (<50, 50-75, 75-90 and >90) and generalized linear models to study the association with overweight, according to the International Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years., Results: The prevalence of overweight at the age of 15 was 9% for children born in 1966 and 16% for children born in 1986. However, medians of infant weight and preschool BMI changed little between the cohorts, and we found similar associations between maternal BMI, infant weight, preschool BMI, and later overweight in the two cohorts. At 5 years, children above the 90th percentile had approximately a 12 times higher risk of being overweight at the age of 15 years compared to children below the 50th percentile in both cohorts., Conclusions: The associations between early body size and adolescent overweight showed remarkable stability, despite the increase in prevalence of overweight over the 20 years between the cohorts. Using consequently defined internal percentiles may be a valuable tool in clinical practice.

Previous studies have suggested that the intake of trans-fatty acids (TFA) plays a role in the development of obesity. The proportions of adipose tissue fatty acids not synthesised endogenously in humans, such as TFA, usually correlate well with the dietary intake. Hence, the use of these biomarkers may provide a more accurate measure of habitual TFA intake than that obtained with dietary questionnaires. The objective of the present study was to investigate the associations between the proportions of specific TFA in adipose tissue and subsequent changes in weight and waist circumference (WC). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50-64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after enrolment. The exposure measures were total trans-octadecenoic acids (18:1t), 18:1 Δ6-10t, vaccenic acid (18:1 Δ11t) and rumenic acid (18:2 Δ9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18:1t was 1.52% (90% central range 0.98, 2.19) in men and 1.47% (1.01, 2.19) in women. No significant associations were observed between the proportions of total 18:1t, 18:1 Δ6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue are not associated with subsequent changes in weight or WC within the exposure range observed in this population.

Background: If preschool measures of body size routinely collected at preventive health examinations are associated with adult central obesity and metabolic syndrome, a focused use of these data for the identification of high risk children is possible. The aim of this study was to test the associations between preschool weight and body mass index (BMI) and adult BMI, central obesity and metabolic alterations., Methods: The Northern Finland Birth Cohort 1966 (NFBC1966) (N = 4111) is a population-based cohort. Preschool weight (age 5 months and 1 year) and BMI (age 2-5 years) were studied in relation to metabolic syndrome as well as BMI, waist circumference, lipoproteins, blood pressure, and fasting glucose at the age of 31 years. Linear regression models and generalized linear regression models with log link were used., Results: Throughout preschool ages, weight and BMI were significantly linearly associated with adult BMI and waist circumference. Preschool BMI was inversely associated with high-density lipoprotein levels from the age of 3 years. Compared with children in the lower half of the BMI range, the group of children with the 5% highest BMI at the age of 5 years had a relative risk of adult obesity of 6.2(95% CI:4.2-9.3), of adult central obesity of 2.4(95% CI:2.0-2.9), and of early onset adult metabolic syndrome of 2.5(95% CI:1.7-3.8)., Conclusions: High preschool BMI is consistently associated with adult obesity, central obesity and early onset metabolic syndrome. Routinely collected measures of body size in preschool ages can help to identify children in need of focused prevention due to their increased risk of adverse metabolic alterations in adulthood.

Introduction: According to the fetal overnutrition hypothesis, obesity in pregnancy predisposes the offspring to obesity. Previous studies have suggested that after biliopancreatic surgery for obesity, the offspring is less likely to be obese. This study aims to further compare the BMI development of children born before and after maternal surgical weight loss., Method: Women with at least one child born before and one child born after bariatric surgery were identified by record-linkage. Information about maternal BMI was extracted from medical records, as was information about the children's BMI from birth to 10 years of age. We retrieved BMI data at four years of age for 340 children, born to 223 women (164 children born before surgery (BS), 176 children born after surgery (AS)). We evaluated prevalence of overweight/obesity and mean BMI in children born BS and AS at the ages of four, six and ten using GEE regression models. For 71 families, where we had complete data on mother and both children, we used a fixed-effects regression model to explore the association between differences in maternal BMI in w10 of the pre- and post-operative pregnancies with siblings' BMI differences at age four., Results: In no age group did we see a significantly reduced prevalence of overweight/obesity AS. For 10-year-old girls, the AS group had significantly higher rates of obesity. There was no association between differences in maternal BMI in early pregnancy and differences in siblings' BMI at four years of age (β = -0.01, CI 95% = -0.11; 0.09)., Conclusions: We have been unable to demonstrate any effect of bariatric surgery on weight development in offspring. It seems unlikely that restrictive bariatric surgery conveys a protective effect in offspring with regards to obesity.

Background: Obesity in late adolescence has been associated with an increased risk of multiple sclerosis (MS); however, it is not known if body size in childhood is associated with MS risk., Methods: Using a prospective design we examined whether body mass index (BMI) at ages 7-13 years was associated with MS risk among 302,043 individuals in the Copenhagen School Health Records Register (CSHRR). Linking the CSHRR with the Danish MS registry yielded 774 MS cases (501 girls, 273 boys). We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Among girls, at each age 7-13 years, a one-unit increase in BMI z-score was associated with an increased risk of MS (HR(age 7)=1.20, 95% CI: 1.10-1.30; HR(age 13)=1.18, 95% CI: 1.08-1.28). Girls who were ≥95(th) percentile for BMI had a 1.61-1.95-fold increased risk of MS as compared to girls <85(th) percentile. The associations were attenuated in boys. The pooled HR for a one-unit increase in BMI z-score at age 7 years was 1.17 (95% CI: 1.09-1.26) and at age 13 years was 1.15 (95% CI: 1.07-1.24)., Conclusion: Having a high BMI in early life is a risk factor for MS, but the mechanisms underlying the association remain to be elucidated.

Background: In the same period as the increasing obesity epidemic, there has been an increased consumption of highly processed foods with a high salt content, and a few studies have suggested that a diet with a high salt content may be associated with obesity., Objective: To investigate the association between 24 h urinary sodium excretion and subsequent change in body weight (BW), waist circumference (WC), body fat (BF) and fat free mass (FFM) among adults., Design: A longitudinal population study based on the Danish part of the MONICA project, with examinations in 1987-1988 and 1993-1994. Complete information on 24 h urinary sodium excretion along with repeated measures of obesity, as well as on potential confounders, was obtained from 215 subjects. Linear regression was used to examine the association between sodium excretion, as a measure of salt consumption, and subsequent changes in BW, WC, BF and FFM, and further evaluated by restricted cubic splines. Stepwise adjustments were made for selected covariates., Results: Neither the crude nor the adjusted models showed any statistically significant associations between sodium excretion and change in BW or WC. Likewise, we found no significant association between sodium excretion and change in BF and FFM in the unadjusted models. However, after adjusting for potential baseline confounders and the concurrent BW change, we found a significant increase in BF of 0.24 kg (P = 0.015, CI: 0.05 to 0.43) per 100 mmol increase in 24 h urinary sodium excretion (equivalent to 6 g of salt), during the 6-year study period. Moreover, during the same period, we found a significant association with FFM of -0.21 kg (P = 0.041, CI: -0.40 to -0.01)., Conclusions: These results suggest that a diet with a high salt content may have a negative influence on development in body composition by expanding BF and reducing FFM.

Background: After the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world., Aim: To examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again., Methods: THE TRENDS IN THE PREVALENCE RATES WERE BASED ON THREE DATA SETS PROVIDING COMPARABLE REPEATED ESTIMATES: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI)., Results: The prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI's from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed., Conclusion: This study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.

Introduction: The NF-κB transcription factor family regulates several genes encoding pro-inflammatory and anti-inflammatory proteins in adipose tissues and in atherosclerotic plaques. The deletion variant allele of the NFKB1 - 94ins/delATTG promoter polymorphism leads to lower transcript levels of the p50 subunit, and the variant allele has been associated with the risk of several inflammatory diseases as well as coronary heart disease where inflammation is important in the pathogenesis. The objective of this study was to explore the potential interaction between the NFKB1-94ins/delATTG promoter polymorphism and general, abdominal, and gluteofemoral obesity in relation to the risk of incident acute coronary syndrome (ACS) in three large independent cohorts., Methods and Results: The analyses were conducted in the Danish prospective study Diet, Cancer and Health and the two US based cohorts; Nurses' Health Study and Health Professionals Follow-up Study. We conducted sex stratified analyses that included 1202 male and 708 female cases of incident ACS. We observed a positive association for general and abdominal obesity with risk of incident ACS, independent of genotype in both genders. Gluteofemoral obesity was negatively associated with ACS risk in women independent of genotype, whereas there was no clear association for men. We calculated the relative excess risk due to interaction (RERI) and observed a statistically significant excess risk among men jointly exposed to general or abdominal obesity and the variant allele of the NFKB1-94ATTG polymorphism, whereas there was a tendency towards sub-additivity for gluteofemoral obesity. The excess risks in all analyses were, however, small and could not clearly be demonstrated in women., Conclusion: The variant allele of the NFKB1-94ins/delATTG promoter polymorphism did not substantially modify the association between obesity and incident ACS.

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.