FTO genotype and weight status among preadolescents: Assessing the mediating effects of obesogenic appetitive traits

Polymorphisms in the Fat Mass and Obesity Associated (FTO) gene are robustly associated with overweight and obesity among children, although the underlying mechanisms are poorly understood. We tested if appetitive traits partially mediated the association between FTO genotype and increased BMI among a sample of US preadolescents. Data were from 178 unrelated 9–10 year olds who participated in an experimental study between 2013 and 2015. Children\u27s DNA was isolated from buccal swabs, and the rs9939609 SNP in the FTO gene was genotyped. Children\u27s age- and sex-adjusted BMI z-scores were computed using height and weight measured at the laboratory. Parents completed the Child Eating Behavior Questionnaire that includes three validated scales of habitual appetitive traits related to drive and regulation: satiety responsiveness, enjoyment of food and food responsiveness. Structural equation modeling was used to assess if those traits mediated the relationship between FTO and BMI z-score. The sample of children was 48.9% male and 91.0% non-Hispanic white. FTO distribution was in Hardy Weinberg equilibrium, and 16.3% of participants were homozygous for the high-risk allele. Mean BMI z-score was greatest among those with the high-risk genotype (ANOVA P \u3c 0.01). In separate structural equation models adjusted for the child\u27s sex and maternal education, decreased satiety responsiveness and increased food responsiveness each partially mediated the positive association between the high-risk genotype and increased BMI z-score (P-value for each indirect effect \u3c0.05). Continued research is needed to better understand how other known genetic obesity risk factors may impact appetitive traits among children

Perceived neighborhood environmental attributes associated with walking and cycling for transport among adult residents of 17 cities in 12 countries: The IPEN study

Introduction: Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions. Objectives: The aim of this study was to examine the strength and shape of the relationship between adults’ neighborhood perceptions and walking and cycling for transport across diverse environments. Methods: As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18–65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire–Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored. Results: Walking-for-transport outcomes were significantly associated with perceived residential density, land use mix–access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix–access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport. Conclusions: Many perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies

Perceived Neighborhood Environmental Attributes Associated with Walking and Cycling for Transport among Adult Residents of 17 Cities in 12 Countries: The IPEN Study

Introduction Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions. Objectives The aim of this study was to examine the strength and shape of the relationship between adults’ neighborhood perceptions and walking and cycling for transport across diverse environments. Methods As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18–65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire–Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored. Results Walking-for-transport outcomes were significantly associated with perceived residential density, land use mix–access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix–access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport. Conclusions Many perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies

Perceived neighborhood environmental attributes associated with walking and cycling for transport among adult residents of 17 cities in 12 countries: the IPEN study

Introduction: Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions. Objectives: The aim of this study was to examine the strength and shape of the relationship between adults’ neighborhood perceptions and walking and cycling for transport across diverse environments. Methods: As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18–65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire–Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored. Results: Walking-for-transport outcomes were significantly associated with perceived residential density, land use mix–access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix–access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport. Conclusions: Many perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies

An \u3cem\u3eFTO\u3c/em\u3e Gene Variant Moderates the Association between Parental Restriction and Child BMI

Objective: This study aimed to explore whether a common variant in the FTO gene moderates the relationship between parental restriction and child BMI. Methods: This study reports on baseline data from 178 parent-child (ages 9–10 years) dyads. Parents completed the Child Feeding Questionnaire and reported on socio-demographic characteristics. Each child’s height, weight and FTO rs9939609 genotype was assessed. Ordinary least squares regression was used to fit the child’s BMI-percentile on parental restriction and the child’s FTO genotype, adjusted for covariates. A likelihood ratio test was used to compare a model with and without a multiplicative interaction term between restriction and genotype. Results: Most participants (93.3%) were white, non-Hispanic. Twenty-three percent of children were overweight/obese and FTO genotype was associated with weight status. Mean parental restriction was statistically higher among overweight/obese vs. normal weight children: 3.3 (SD 0.8) vs. 2.8 (SD 1.0); t-test p-value = 0.002. Parental restriction was positively associated with child BMI-percentile and BMI-z only among children with two copies of the high-risk FTO allele (p for interaction = 0.02), where each one-point increase in parental restriction was associated with a 14.7 increase in the child’s BMI-percentile or a 0.56-point increase in the child’s BMI z-score. Conclusion: For only the children with two high-risk alleles, parental restriction was positively associated with child BMI-percentile

Altered gene expression and DNA damage in peripheral blood cells from Friedreich's ataxia patients: Cellular model of pathology

The neurodegenerative disease Friedreich's ataxia (FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p<0.0001, respectively). Additionally, frataxin mRNA levels correlated with age of onset of disease and displayed unique sets of gene alterations involved in immune response, oxidative phosphorylation, and protein synthesis. Many of the key pathways observed by transcription profiling were downregulated, and we believe these data suggest that patients with prolonged frataxin deficiency undergo a systemic survival response to chronic genotoxic stress and consequent DNA damage detectable in blood. In conclusion, our results yield insight into the nature and progression of FRDA, as well as possible therapeutic approaches. Furthermore, the identification of potential biomarkers, including the DNA damage found in peripheral blood, may have predictive value in future clinical trials

Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer

To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. Patients included 3215 women diagnosed with early stage breast cancer (Stage I &gt; 1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors. Neither moderate (5-10%) nor large (&gt; 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis). Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor