Neighborhood Street Scale Elements,Sedentary Time and Cardiometabolic Risk Factors in Inactive Ethnic Minority Women

Background

Cardiometabolic risk factors such as obesity, excess percent body fat, high blood pressure, elevated resting heart rate and sedentary behavior have increased in recent decades due to changes in the environment and lifestyle. Neighborhood micro-environmental, street scale elements may contribute to health above and beyond individual characteristics of residents.

Purpose

To investigate the relationship between neighborhood street scale elements and cardiometabolic risk factors among inactive ethnic minority women.

Method

Women (N = 410) completed measures of BMI, percent body fat, blood pressure, resting heart rate, sedentary behavior and demographics. Trained field assessors completed the Pedestrian Environment Data Scan in participants’ neighborhoods. Data were collected from 2006–2008. Multiple regression models were conducted in 2011 to estimate the effect of environmental factors on cardiometabolic risk factors.

Results

Adjusted regression models found an inverse association between sidewalk buffers and blood pressure, between traffic control devices and resting heart rate, and a positive association between presence of pedestrian crossing aids and BMI (ps<.05). Neighborhood attractiveness and safety for walking and cycling were related to more time spent in a motor vehicle (ps<.05).

Conclusions

Findings suggest complex relationships among micro-environmental, street scale elements that may confer important cardiometabolic benefits and risks for residents. Living in the most attractive and safe neighborhoods for physical activity may be associated with longer times spent sitting in the car.     

Accelerometry‐Measured Activity or Sedentary Time and Overweight in Rural Boys and Girls

Objective: The aim of this study was to examine the association between overweight and physical activity or sedentary time measured by accelerometry in rural boys and girls 7 to 19 years old. Research Methods and Procedures: A cross‐sectional study was conducted involving 130 girls and 99 boys in elementary, middle, and high school in rural Maryland. After weight, height, and body composition were measured, children wore an Actiwatch accelerometer for 6 days. Comparisons for activity counts were made between normal and overweight or at risk for overweight (at‐risk/overweight) participants (≥85th percentile of BMI). The associations between body composition and accelerometry‐defined activity levels (sedentary, light, moderate, and vigorous) were analyzed by age group for boys and girls. Results: Differences in total activity in counts per day or counts per minute were not observed between normal and at‐risk/overweight boys or girls in all age groups. No associations between measures of body composition and time spent in an activity level were seen in boys. Fat mass and percentage fat were positively correlated to time spent in sedentary activity (range r = 0.42 to 0.54, all p < 0.01) for girls. In contrast, fat mass and percentage fat were negatively related to time spent in light activity (range, r = ?0.40 to ?0.51, p < 0.05) for girls. Discussion: In girls, but not boys, greater body fat is associated with greater time spent being inactive, and lower levels of body fat are associated with more time spent in light activity. Physical activity interventions targeting inactive children in rural communities are warranted.     

Correlation between Serum Resistin Level and Adiposity in Obese Individuals

Objective: Resistin is associated with insulin resistance in mice and may play a similar role in humans. The aim of our study was to examine the relationship of serum resistin level to body composition, insulin resistance, and related obesity phenotypes in humans. Research Methods and Procedures: Sixty‐four young (age 32 ± 10 years), obese (BMI 32.9 ± 5.6), nondiabetic subjects taking no medication, and 15 lean (BMI 21.1 ± 1.3) volunteers were studied cross‐sectionally. Thirty‐five of the subjects were also reevaluated after 1.5 years on a weight reduction program entailing dieting and exercise; changes of serum resistin were compared with changes of BMI, body composition, fat distribution, and several indices of insulin sensitivity derived from plasma glucose and serum insulin levels measured during 75‐g oral glucose tolerance test. Results: In a cross‐sectional analysis, serum resistin was significantly higher in obese subjects than in lean volunteers (24.58 ± 12.93 ng/mL; n = 64 vs. 12.83 ± 8.30 ng/mL; n = 15; p < 0.01), and there was a correlation between resistin level and BMI, when the two groups were combined (ρ = 0.35, p < 0.01). Although cross‐sectional analysis in obese subjects revealed no correlation between serum resistin and parameters related to adiposity or insulin resistance, longitudinal analysis revealed change in serum resistin to be positively correlated with changes in BMI, body fat, fat mass, visceral fat area, and mean glucose and insulin (ρ = 0.39, 0.40, 0.44, 0.50, 0.40, and 0.50; p = 0.02, 0.03, 0.02, <0.01, 0.02, and <0.01, respectively). Discussion: Resistin appears to be related to human adiposity and to be a possible candidate factor in human insulin resistance.     

Gangliosides of Active and Inactive Neuroblastoma Clones

It is possible to divide neuroblastoma cells into clones able to synthesize neurotransmitters (active clones) or not (inactive clones).
The analysis of gangliosides of active and inactive clones shows that their total lipid sialic acids is markedly lower than that of neuron-enriched fractions prepared from brain. The ganglioside pattern of the cultured cells also differs notably from those obtained with neuronal fractions from brain. The absence of tri- and tetrasialogangliosides and the presence of appreciable amounts of the simplest monosialogangliosides are particularly noticeable in the neuroblastoma. Morphological differentiation obtained by serum deprivation, dibutyryl cyclic AMP or bromodeoxyuridine does not restore a true neuronal pattern. Gangliosides could not therefore be used as a marker of neuronal differentiation in this type of cell. No correlations can be found between the ganglioside pattern and the ability of cells to synthesize neurotransmitters.     

Pigment Epithelium‐Derived Factor,Insulin Sensitivity,and Adiposity in Polycystic Ovary Syndrome: Impact of Exercise Training

Pigment epithelium‐derived factor (PEDF) is upregulated in obese rodents and is involved in the development of insulin resistance (IR). We aim to explore the relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular risk factors in obese women with polycystic ovary syndrome (PCOS) and weight‐matched controls and to examine the impact of endurance exercise training on PEDF. This prospective cohort intervention study was based at a tertiary medical center. Twenty obese PCOS women and 14 non‐PCOS weight‐matched women were studied at baseline. PEDF, cardiometabolic markers, detailed body composition, and euglycemic—hyperinsulinemic clamps were performed and measures were repeated in 10 PCOS and 8 non‐PCOS women following 12 weeks of intensified aerobic exercise. Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to controls (175.6 ± 96.3 and 257.2 ± 64.3 mg.m^?2.min^?1) at baseline, yet both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR (r = ?0.41, P = 0.03) and high‐density lipoprotein (HDL) (r = ?0.46, P = 0.01), and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P = 0.004). The correlation with GIR was not significant after adjusting for fat mass (P = 0.07). Exercise training maintained BMI and increased GIR in both groups; however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is not associated with IR when adjusted for fat mass, and is not reduced by endurance exercise training despite improved insulin sensitivity. PEDF was associated with cardiovascular risk factors, suggesting PEDF may be a marker of cardiovascular risk status.     

Distinct Recycling of Active and Inactive β1 Integrins

Integrin trafficking plays an important role in cellular motility and cytokinesis. Integrins undergo constant endo/exocytic shuttling to facilitate the dynamic regulation of cell adhesion. Integrin activity toward the components of the extracellular matrix is regulated by the ability of these receptors to switch between active and inactive conformations. Several cellular signalling pathways have been described in the regulation of integrin traffic under different conditions. However, the interrelationship between integrin activity conformations and their endocytic fate have remained incompletely understood. Here, we have investigated the endocytic trafficking of active and inactive β1 integrins in cancer cells. Both conformers are endocytosed in a clathrin‐ and dynamin‐dependent manner. The net endocytosis rate of the active β1 integrins is higher, whereas endocytosis of the inactive β1 integrin is counteracted by rapid recycling back to the plasma membrane via an ARF 6‐ and early endosome antigen 1‐positive compartment in an Rab 4a‐ and actin‐dependent manner. Owing to these distinct trafficking routes, the two receptor pools display divergent subcellular localization. At steady state, the inactive β1 integrin is mainly on the plasma membrane, whereas the active receptor is predominantly intracellular. These data provide new insights into the endocytic traffic of integrins and imply the possibility of a previously unappreciated crosstalk between pathways regulating integrin activity and traffic.     

Associations of Sedentary Behavior,Sedentary Bouts and Breaks in Sedentary Time with Cardiometabolic Risk in Children with a Family History of Obesity

Background

Although reports in adults suggest that breaks in sedentary time are associated with reduced cardiometabolic risk, these findings have yet to be replicated in children.

Purpose

To investigate whether objectively measured sedentary behavior, sedentary bouts or breaks in sedentary time are independently associated with cardiometabolic risk in a cohort of Canadian children aged 8–11 years with a family history of obesity.

Methods

Data from 286 boys and 236 girls living in Quebec, Canada, with at least one biological parent with obesity (QUALITY cohort) were collected from 2005–2008, and analyzed in 2013. Sedentary behavior, light and moderate-to-vigorous physical activity were measured over 7 days using accelerometry. Leisure time computer/video game use and TV viewing over the past 7 days were self-reported. Outcomes included waist circumference, body mass index Z-score, fasting insulin, fasting glucose, triglycerides, HDL-cholesterol, C-reactive protein and a continuous cardiometabolic risk score.

Results

After adjustment for confounders, breaks in sedentary time and the number of sedentary bouts lasting 1–4 minutes were associated with reduced cardiometabolic risk score and lower BMI Z-score in both sexes (all p<0.05). The number of sedentary bouts lasting 5–9 minutes was negatively associated with waist circumference in girls only, while the number of bouts lasting 10–14 minutes was positively associated with fasting glucose in girls, and with BMI Z-score in boys (all p<0.05). Leisure time computer/video game use was associated with increased cardiometabolic risk score and waist circumference in boys, while TV viewing was associated with increased cardiometabolic risk, waist circumference, and BMI Z-score in girls (all p<0.05).

Conclusions

These results suggest that frequent interruptions in sedentary time are associated with a favourable cardiometabolic risk profile and highlight the deleterious relationship between screen time and cardiometabolic risk among children with a family history of obesity.     

Differential Binding of Active and Inactive Integrin to Talin

Bi-directional signaling of integrins plays an important role in platelet and leukocyte function. Talin plays a key role in integrin bi-directional signaling and its binding to integrin is highly regulated. The precise regulation of the recruitment and binding of talin to integrin is still being elucidated. In particular, the recruitment of talin to integrin is controlled by the RAP-1 and RIAM/lamellipodin signaling axis and the affinity between talin and integrin is regulated by the conformation or protease cleavage of talin. However, whether the binding between integrin and talin is also regulated by integrin conformation has not been thoroughly explored before. In this work, we used biochemical binding assays to study the potential role of integrin conformational changes in integrin–talin interactions. Constitutively active integrin αIIbb3 binds markedly stronger to talin than inactive αIIbb3. Inactive αIIbb3 markedly increases its binding to talin once activated, regardless of how αIIbb3 is activated. Further, the increased binding to talin is b3 tail dependent. Our results suggest that integrin conformation is another regulatory mechanism for integrin–talin interaction.     

Energy Expenditure and Adiposity in Nigerian and African‐American Women

Objective: Obesity is a prevalent condition in industrialized societies and is increasing around the world. We sought to assess the relative importance of resting energy expenditure (REE) and activity EE (AEE) in two populations with different rates of obesity. Methods and Procedures: Women of African descent between 18 and 59 years of age were recruited from rural Nigeria and from metropolitan Chicago. Total EE (TEE) was measured using the doubly labeled water (DLW) technique and REE by indirect calorimetry; AEE was calculated as the difference between TEE and the sum of REE plus a factor for the thermic effect of food. In the analyses all EE parameters were adjusted for body size using a regression method. Comparisons were made between the groups and associations between EE and adiposity examined. Results: A total of 149 Nigerian and 172 African‐American women completed the protocol. All body size measurements were lower in the Nigerian women. Adjusted TEE and REE were higher in the Nigerian cohort but adjusted AEE did not differ significantly. Adjustment for parity, seasonality, and recent illness did not modify mean AEE or adiposity. In neither cohort was there a meaningful association between measures of AEE and adiposity. Discussion: In these cohorts of women from very different environments, AEE did not differ significantly nor was it associated cross‐sectionally with adiposity. If generalizable, these findings suggest that reduction in AEE may have less of a role in the development of obesity than anticipated. The possibility remains that variation in type and duration of activity plays a role not captured by total AEE.     

Apolipoprotein A‐II Polymorphism and Visceral Adiposity in African‐American and White Women

To determine the association between the ?265 T to C substitution in the apolipoprotein A‐II (APOA‐II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African‐American and white women, we genotyped 237 women (115 African‐American and 122 white) for this polymorphism. Body composition was assessed by DXA, and VAT was determined from a single computed tomography scan. In addition to VAT, we examined the association between the polymorphism and other phenotypes (total body fat, total abdominal adipose tissue, and subcutaneous abdominal adipose tissue). The mutant C allele in the APOA‐II gene was less frequent in African‐American compared with white women, 23% vs. 36%, respectively (p < 0.01). VAT was significantly higher in carriers of the C allele compared with noncarriers after adjustment for total body fat (p < 0.05). When separate analyses by ethnic group were conducted, the association between the polymorphism and VAT was observed in white (p < 0.05) but not African‐American (p = 0.57) women. There was no association between the polymorphism and the other phenotypes. These results indicate a significant association between the T265C APOA‐II polymorphism and levels of VAT in premenopausal women. This association is present in white but not African‐American women.     

The Flight Apparatus of Migratory and Sedentary Individuals of a Partially Migratory Songbird Species

Variations in the geometry of the external flight apparatus of birds are beneficial for different behaviors. Long-distance flight is less costly with more pointed wings and shorter tails; however these traits decrease maneuverability at low speeds. Selection has led to interspecific differences in these and other flight apparatuses in relation to migration distance. If these principles are general, how are the external flight apparatus within a partially migratory bird species shaped in which individuals either migrate or stay at their breeding grounds? We resolved this question by comparing the wing pointedness and tail length (relative to wing length) of migrant and resident European blackbirds (Turdus merula) breeding in the same population. We predicted that migrant blackbirds would have more pointed wings and shorter tails than residents. Contrary to our predictions, there were no differences between migrants and residents in either measure. Our results indicate that morphological differences between migrants and residents in this partially migratory population may be constrained.     

Consuming Fructose‐sweetened Beverages Increases Body Adiposity in Mice

Objective: The marked increase in the prevalence of obesity in the United States has recently been attributed to the increased fructose consumption. To determine if and how fructose might promote obesity in an animal model, we measured body composition, energy intake, energy expenditure, substrate oxidation, and several endocrine parameters related to energy homeostasis in mice consuming fructose. Research Methods and Procedures: We compared the effects of ad libitum access to fructose (15% solution in water), sucrose (10%, popular soft drink), and artificial sweetener (0% calories, popular diet soft drink) on adipogenesis and energy metabolism in mice. Results: Exposure to fructose water increased adiposity, whereas increased fat mass after consumption of soft drinks or diet soft drinks did not reach statistical significance (n = 9 each group). Total intake of energy was unaltered, because mice proportionally reduced their caloric intake from chow. There was a trend toward reduced energy expenditure and increased respiratory quotient, albeit not significant, in the fructose group. Furthermore, fructose produced a hepatic lipid accumulation with a characteristic pericentral pattern. Discussion: These data are compatible with the conclusion that a high intake of fructose selectively enhances adipogenesis, possibly through a shift of substrate use to lipogenesis.     

Objectively Measured Total and Occupational Sedentary Time in Three Work Settings

Background

Sedentary behaviour increases the risk for morbidity. Our primary aim is to determine the proportion and factors associated with objectively measured total and occupational sedentary time in three work settings. Secondary aim is to study the proportion of physical activity and prolonged sedentary bouts.

Methods

Data were obtained using ActiGraph accelerometers from employees of: 1) a financial service provider (n = 49 men, 31 women), 2) two research institutes (n = 30 men, 57 women), and 3) a construction company (n = 38 men). Total (over the whole day) and occupational sedentary time, physical activity and prolonged sedentary bouts (lasting ≥30 minutes) were calculated by work setting. Linear regression analyses were performed to examine general, health and work-related factors associated with sedentary time.

Results

The employees of the financial service provider and the research institutes spent 76–80% of their occupational time in sedentary behaviour, 18–20% in light intensity physical activity and 3–5% in moderate-to-vigorous intensity physical activity. Occupational time in prolonged sedentary bouts was 27–30%. Total time was less sedentary (64–70%), and had more light intensity physical activity (26–33%). The employees of the construction company spent 44% of their occupational time in sedentary behaviour, 49% in light, and 7% in moderate intensity physical activity, and spent 7% in sedentary bouts. Total time spent in sedentary behavior was 56%, 40% in light, and 4% in moderate intensity physical behaviour, and 12% in sedentary bouts. For women, low to intermediate education was the only factor that was negatively associated with occupational sedentary time.

Conclusions

Sedentary behaviour is high among white-collar employees, especially in highly educated women. A relatively small proportion of sedentary time was accrued in sedentary bouts. It is recommended that worksite health promotion efforts should focus on reducing sedentary behaviour through improving light intensity physical activity.     

Active and Inactive Cdc42 Differ in Their Insert Region Conformational Dynamics

Cell division control protein 42 homolog (Cdc42) protein, a Ras superfamily GTPase, regulates cellular activities, including cancer progression. Using all-atom molecular dynamics (MD) simulations and essential dynamic analysis, we investigated the structure and dynamics of the catalytic domains of GDP-bound (inactive) and GTP-bound (active) Cdc42 in solution. We discovered substantial differences in the dynamics of the inactive and active forms, particularly in the “insert region” (residues 122–135), which plays a role in Cdc42 activation and binding to effectors. The insert region has larger conformational flexibility in the GDP-bound Cdc42 than in the GTP-bound Cdc42. The G2 loop and switch I at the effector lobe of the catalytic domain exhibit large conformational changes in both the GDP- and the GTP-bound systems, but in the GTP-bound Cdc42, the switch I interactions with GTP are retained. Oncogenic mutations were identified in the Ras superfamily. In Cdc42, the G12V and Q61L mutations decrease the GTPase activity. We simulated these mutations in both GDP- and GTP-bound Cdc42. Although the overall structural organization is quite similar between the wild type and the mutants, there are small differences in the conformational dynamics, especially in the two switch regions. Taken together, the G12V and Q61L mutations may play a role similar to their K-Ras counterparts in nucleotide binding and activation. The conformational differences, which are mainly in the insert region and, to a lesser extent, in the switch regions flanking the nucleotide binding site, can shed light on binding and activation. We propose that the differences are due to a network of hydrogen bonds that gets disrupted when Cdc42 is bound to GDP, a disruption that does not exist in other Rho GTPases. The differences in the dynamics between the two Cdc42 states suggest that the inactive conformation has reduced ability to bind to effectors.     

Stress and Adiposity: A Meta‐Analysis of Longitudinal Studies

Psychosocial stress has been strongly implicated in the biology of adiposity but epidemiological studies have produced inconsistent results. The aim of this analysis was to bring together results from published, longitudinal, prospective studies examining associations between psychosocial stress and objectively measured adiposity in a meta‐analysis. Searches were conducted on Medline, PsycINFO, Web of Science, and PubMed (to January 2009) and reference lists from relevant articles were examined. Prospective studies relating psychosocial stress (general life stress (including caregiver stress), work stress) to BMI, body fat, body weight, waist circumference, or waist‐to‐hip ratio were included. Analyses from 14 cohorts were collated and evaluated. There was no significant heterogeneity, no evidence of publication bias, and no association between study quality and outcomes. The majority of analyses found no significant relationship between stress and adiposity (69%), but among those with significant effects, more found positive than negative associations (25 vs. 6%). Combining results in a meta‐analysis showed that stress was associated with increasing adiposity (r = 0.014; confidence interval (CI) = 0.002–0.025, P < 0.05). Effects were stronger for men than women, in analyses with longer rather than shorter follow‐ups, and in better quality studies. We conclude that psychosocial stress is a risk factor for weight gain but effects are very small. Variability across studies indicates there are moderating variables to be elucidated.