Effects of a School-Based Gardening, Cooking, and Nutrition Cluster Randomized Controlled Trial on Unprocessed and Ultra-Processed Food Consumption.

BACKGROUND: School-based gardening and nutrition education interventions report improvements in dietary intake, notably through fruit and vegetables. However, gardening, cooking, and nutrition randomized controlled trials are limited in evaluating dietary quality, and none have examined processed food consumption to date. OBJECTIVES: The study examined the effects of Texas Sprouts (TX Sprouts), a gardening, cooking, and nutrition education intervention, compared with control on unprocessed and ultra-processed food (UPF) consumption in predominately low-income Hispanic children. METHODS: TX Sprouts was a school-based cluster randomized controlled trial that consisted of 16 elementary schools randomly assigned to either the TX Sprouts intervention (n = 8 schools) or control (delayed intervention; n = 8 schools) over 3 y (2016-2019). TX Sprouts schools received an outdoor teaching garden and 18 1-h lessons taught by trained educators throughout the school year. Dietary intake data via 2 24-h dietary recalls were collected on a random subsample (n = 468) at baseline and postintervention. All foods and beverages were categorized using the NOVA food classification system (e.g., unprocessed, processed, ultra-processed). Generalized linear mixed effects modeling tested changes in percent calories and grams of NOVA groups between the intervention and control estimates with schools as random clusters. RESULTS: Of the sample, 63% participated in the free and reduced-price lunch program, and 57% were Hispanic, followed by non-Hispanic White (21%) and non-Hispanic Black (12%). The intervention, compared to the control, resulted in an increase in consumption of unprocessed foods (2.3% compared with -1.8% g; P < 0.01) and a decrease in UPF (-2.4% compared with 1.4% g; P = 0.04). In addition, Hispanic children in the intervention group had an increase in unprocessed food consumption and a decrease in UPF consumption compared to non-Hispanic children (-3.4% compared with 1.5% g; P < 0.05). CONCLUSIONS: Study results suggest that school-based gardening, cooking, and nutrition education interventions can improve dietary intake, specifically increasing unprocessed food consumption and decreasing UPF consumption. This trial was registered at clinicaltrials.gov as NCT02668744.

Breakfast Consumption May Improve Fasting Insulin, HOMA-IR, and HbA1c Levels in Predominately Low-Income, Hispanic Children 7-12 Years of Age.

Children from low-income households and minority families have high cardiometabolic risk. Although breakfast consumption is known to improve cardiometabolic health in children, limited randomized control trials (RCT) have explored this association in low-income and racial/ethnic U.S. minority families. This study conducted secondary analyses from TX Sprouts, a school-based gardening, cooking, and nutrition education RCT, to examine the intervention effect on breakfast consumption and how changes in breakfast consumption impact cardiometabolic risk in predominately low-income, multi-ethnic children. TX Sprouts consisted of 16 schools (8 intervention; 8 control) in greater Austin, TX. A total of 18 lessons were taught, including topics on breakfast consumption benefits and choosing healthy food options at school. Children completed clinical measures (e.g., anthropometrics, body composition via bioelectrical impedance), and the number of breakfast occasions (BO) per week (at home and school) was captured via validated survey at baseline and post-intervention. Post-study­Baseline changes in breakfast consumption were used to categorize students as: maintainers (BO −1 to 1 day/week), decreasers (BO ≤−2 day/week), and increasers (BO ≥2 day/week). Optional fasting blood draws were performed on a subsample. Generalized weighted linear mixed modeling tested differences between intervention and control, with schools as random clusters. Analysis of covariance and linear regression examined changes in breakfast consumption on cardiometabolic outcomes, controlling for age, sex, race/ethnicity, free and reduced-price school meal participation (FRL), school site, breakfast location, physical activity, baseline cardiometabolic measures, and BMI z-score. This study included 1417 children (mean age 9 years; 53% male; 58% Hispanic, 63% FRL; breakfast consumption patterns: 63% maintainers, 16% decreasers, and 21% increasers). There was no intervention effect on changes in breakfast consumption. Compared to decreasers, increasers had an increase in insulin (−0.3 µIU/mL vs. +4.1 µIU/mL; p = 0.01) and a larger increase in HOMA-IR (+0.4 vs. +1.5; p < 0.01). Every one-day increase in breakfast consumption decreased fasting insulin by 0.44 µIU/mL, HOMA-IR by 0.11, and hemoglobin A1c by 0.01% (p ≤ 0.03). Increased breakfast consumption was linked to improved glucose control, suggesting breakfast can mitigate risk in a high-risk population. To better understand underlying mechanisms linking breakfast consumption to improved metabolic health, RCTs focusing on breakfast quality and timing are warranted.

Distinct racial and ethnic metabolic syndrome characteristics: A comparative assessment in low-income children 7-10 years of age.

BACKGROUND: Pediatric MetS prevalence varies due to lack of consensus on evaluative criteria and associated thresholds, with most not recommending a diagnosis <10 years. However, MetS risk components are becoming evident earlier in life and affect races and ethnicities disproportionately. OBJECTIVES: To compare the prevalence of MetS based on existing definitions and elucidate racial- and ethnic-specific characteristics associated with MetS prevalence. METHODS: The baseline and follow-up samples included 900 and 557 children 7-10 years, respectively. Waist circumference, BMI percentile, blood pressure, fasting plasma glucose (FPG), insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured. Agreement between MetS definitions was quantified via kappa statistics. MetS and risk factor prevalence and the predictability of metabolic parameters on MetS eight months later was evaluated via logistic regression. McFadden pseudo-R2 was reported as a measure of predictive ability, and the Akaike information criterion evaluated fit of each model. RESULTS: The baseline sample was 55.0% male and 71.6% Hispanic, followed by non-Hispanic White (NHW) (17.3%) and non-Hispanic Black (NHB) (11.1%), with an average age of 9.2 years. MetS prevalence ranged from 7.6% to 21.4%, highest in Hispanic (9.0%-24.0%) and lowest in NHB children (4.0%-14.0%). Highest agreement was between Ford et al. and Cook et al. definitions (K = 0.88) and lowest agreements were consistently with the International Diabetes Federation criteria (K ≤ 0.57). Compared to NHW children, Hispanic children had higher odds for MetS (OR: 1.7; p = 0.03) and waist circumference, HDL-C, and FPG risk factors (p < 0.05), while NHB children had higher odds for the FPG risk factor (p ≤ 0.007) and lower odds for the plasma triglycerides risk factor (p = 0.002), across multiple MetS definitions. In longitudinal analyses, HDL-C was the strongest independent predictor of MetS in Hispanic and NHW children (p < 0.001 and p < 0.01, respectively), while plasma triglycerides was the strongest independent predictor of MetS in NHB children (p < 0.05). CONCLUSIONS: MetS prevalence was high in children ≤10 years, and proposed criteria are susceptible to racial and ethnic bias, diagnosing some populations more than other populations with high cardiovascular risk. Earlier preventative measures should be imposed in clinical settings, accounting for racial and ethnic differences, to mitigate disease onset.

Comparison of School vs Home Breakfast Consumption with Cardiometabolic and Dietary Parameters in Low-Income, Multiracial/Ethnic Elementary School-Aged Children.

BACKGROUND: Breakfast consumption is often associated with improving cardiometabolic parameters and diet quality. However, literature evaluating breakfast consumption with these outcomes between the school and home environments is limited. OBJECTIVE: This study examined relationships between breakfast consumption locations (school vs home) and cardiometabolic parameters, breakfast dietary intake, and daily dietary intake. DESIGN: This cross-sectional study used baseline data from TX Sprouts, a 1-year school-based gardening, nutrition, and cooking cluster-randomized trial, implemented in 16 elementary schools in Austin, TX, during 2016 to 2019. PARTICIPANTS/SETTING: Analyses included 383 low-income, multiracial/ethnic elementary school-aged children (mean age = 9.2 years; 60.6% Hispanic; 70.5% free/reduced lunch; 58.5% home breakfast consumers). MAIN OUTCOME MEASURES: Cardiometabolic parameters were obtained via fasting blood draws, and dietary intake was assessed using one 24-hour dietary recall conducted on a random, unannounced weekday. Cardiometabolic and dietary parameters (ie, energy intake, macronutrients, and food group servings) for breakfast and for the day were evaluated. STATISTICAL ANALYSES PERFORMED: Multivariate analysis of covariance was performed to examine cardiometabolic parameters and dietary intake between school and home breakfasts. RESULTS: School breakfast consumers (SBC) had lower fasting triglyceride levels than home breakfast consumers (HBC) (89.0 mg/dL vs 95.7 mg/dL; P = 0.03) (to convert to mmol/L, multiply by 0.0113). SBC had lower total fat for the day (P = 0.02) and lower total and saturated fat, sodium, and refined grains at breakfast (P ≤ 0.01) than HBC. However, SBC had lower protein at breakfast (P = 0.01) and higher carbohydrates, total sugar, and added sugar for the day and at breakfast (P ≤ 0.03) than HBC. CONCLUSIONS: SBC compared with HBC had lower fat intake, which may have contributed to the lower triglyceride level observed in SBC, but also had lower protein intake at breakfast and higher added sugar intake for the day and at breakfast. These results suggest dietary intake differed between HBC and SBC; that is, the home and school environments, but more research is needed to evaluate if such differences are due to School Breakfast Program guidelines.

Circadian rhythms and the gut microbiome synchronize the host's metabolic response to diet.

The molecular circadian clock and symbiotic host-microbe relationships both evolved as mechanisms that enhance metabolic responses to environmental challenges. The gut microbiome benefits the host by breaking down diet-derived nutrients indigestible by the host and generating microbiota-derived metabolites that support host metabolism. Similarly, cellular circadian clocks optimize organismal physiology to the environment by influencing the timing and coordination of metabolic processes. Host-microbe interactions are influenced by dietary quality and timing, as well as daily light/dark cycles that entrain circadian rhythms in the host. Together, the gut microbiome and the molecular circadian clock play a coordinated role in neural processing, metabolism, adipogenesis, inflammation, and disease initiation and progression. This review examines the bidirectional interactions between the circadian clock, gut microbiota, and host metabolic systems and their effects on obesity and energy homeostasis. Directions for future research and the development of therapies that leverage these systems to address metabolic disease are highlighted.

The potential of digital phenotyping to advance the contributions of mobile health to self-management science.

Digital phenotyping consists of moment-by-moment quantification of behavioral data from individual people, typically collected passively from smartphones and other sensors. Within the evolving context of precision health, digital phenotyping can advance the use of mobile health -based self-management tools and interventions by enabling more accurate prediction for prevention and treatment, facilitating supportive strategies, and informing the development of features to motivate self-management behaviors within real-world conditions. This represents an advancement in self-management science: with digital phenotyping, nurse scientists have opportunities to tailor interventions with increased precision. In this paper, we discuss the emergence of digital phenotyping, the historical background of ecological momentary assessment, and the current state of the science of digital phenotyping, with implications for research design, computational requirements, and ethical considerations in self-management science, as well as limitations.

The influence of 15-week exercise training on dietary patterns among young adults.

BACKGROUND/OBJECTIVES: Little is currently known about how exercise may influence dietary patterns and/or food preferences. The present study aimed to examine the effect of a 15-week exercise training program on overall dietary patterns among young adults. SUBJECTS/METHODS: This study consisted of 2680 young adults drawn from the Training Intervention and Genetics of Exercise Response (TIGER) study. Subjects underwent 15 weeks of aerobic exercise training, and exercise duration, intensity, and dose were recorded for each session using computerized heart rate monitors. In total, 4355 dietary observations with 102 food items were collected using a self-administered food frequency questionnaire before and after exercise training (n = 2476 at baseline; n = 1859 at 15 weeks). Dietary patterns were identified using a Bayesian sparse latent factor model. Changes in dietary pattern preferences were evaluated based on the pre/post-training differences in dietary pattern scores, accounting for the effects of gender, race/ethnicity, and BMI. RESULTS: Within each of the seven dietary patterns identified, most dietary pattern scores were decreased following exercise training, consistent with increased voluntary regulation of food intake. A longer duration of exercise was associated with decreased preferences for the western (ß: -0.0793; 95% credible interval: -0.1568, -0.0017) and snacking (ß: -0.1280; 95% credible interval: -0.1877, -0.0637) patterns, while a higher intensity of exercise was linked to an increased preference for the prudent pattern (ß: 0.0623; 95% credible interval: 0.0159, 0.1111). Consequently, a higher dose of exercise was related to a decreased preference for the snacking pattern (ß: -0.0023; 95% credible interval: -0.0042, -0.0004) and an increased preference for the prudent pattern (ß: 0.0029; 95% credible interval: 0.0009, 0.0048). CONCLUSIONS: The 15-week exercise training appeared to motivate young adults to pursue healthier dietary preferences and to regulate their food intake.

Advanced Dietary Patterns Analysis Using Sparse Latent Factor Models in Young Adults.

Background: Principal components analysis (PCA) has been the most widely used method for deriving dietary patterns to date. However, PCA requires arbitrary ad hoc decisions for selecting food variables in interpreting dietary patterns and does not easily accommodate covariates. Sparse latent factor models can be utilized to address these issues. Objective: The objective of this study was to compare Bayesian sparse latent factor models with PCA for identifying dietary patterns among young adults. Methods: Habitual food intake was estimated in 2730 sedentary young adults from the Training Interventions and Genetics of Exercise Response (TIGER) Study [aged 18-35 y; body mass index (BMI; in kg/m2): 26.5 ± 6.1] who exercised <30 min/wk during the previous 30 d without restricting caloric intake before study enrollment. A food-frequency questionnaire was used to generate the frequency intakes of 102 food items. Sparse latent factor modeling was applied to the standardized food intakes to derive dietary patterns, incorporating additional covariates (sex, race/ethnicity, and BMI). The identified dietary patterns via sparse latent factor modeling were compared with the PCA derived dietary patterns. Results: Seven dietary patterns were identified in both PCA and sparse latent factor analysis. In contrast to PCA, the sparse latent factor analysis allowed the covariate information to be jointly accounted for in the estimation of dietary patterns in the model and offered probabilistic criteria to determine the foods relevant to each dietary pattern. The derived patterns from both methods generally described common dietary behaviors. Dietary patterns 1-4 had similar food subsets using both statistical approaches, but PCA had smaller sets of foods with more cross-loading elements between the 2 factors. Overall, the sparse latent factor analysis produced more interpretable dietary patterns, with fewer of the food items excluded from all patterns. Conclusion: Sparse latent factor models can be useful in future studies of dietary patterns by reducing the intrinsic arbitrariness involving the choice of food variables in interpreting dietary patterns and incorporating covariates in the assessment of dietary patterns.

A High-Fat Compared with a High-Carbohydrate Breakfast Enhances 24-Hour Fat Oxidation in Older Adults.

Background: The ability to oxidize fat is associated with a lower risk of chronic metabolic disease. Preclinical data in mice showed that a high-fat "breakfast" increased 24-h fat oxidation relative to a high-carbohydrate breakfast. Objectives: The objectives of this study were to determine whether the timing of macronutrient intake in humans affects daily fuel utilization and to examine associations between fuel utilization and metabolic indexes. Methods: Participants were 29 healthy sedentary men and women (aged 55-75 y) with a body mass index (kg/m2) between 25 and 35. Participants were randomly assigned to receive either a high-fat breakfast (FB; 35% carbohydrate, 20% protein, 45% fat; n = 13) or a high-carbohydrate breakfast (CB; 60% carbohydrate, 20% protein, 20% fat; n = 16) for 4 wk while consuming a "neutral" lunch and dinner. Twenty-four-hour and postprandial respiratory quotients (RQs) were measured by whole-room indirect calorimetry. Insulin and glucose measures including insulin sensitivity were determined by an oral-glucose-tolerance test. Measures were taken at baseline and after the 4-wk intervention. Group-by-time interactions were determined by 2-factor repeated-measures mixed-model ANOVA. Pearson's correlation analyses were used to determine associations of 24-h RQs with metabolic measures after the intervention. Results: There was a significant group-by-time interaction for change in the 24-h RQ [FB (mean ± SD): 0.88 ± 0.02 to 0.86 ± 0.02; CB: 0.88 ± 0.02 for both; P < 0.05], breakfast RQ (FB: 0.88 ± 0.03 to 0.86 ± 0.03; CB: 0.89 ± 0.02 to 0.90 ± 0.02; P < 0.01), and lunch RQ (FB: 0.089 ± 0.03 to 0.85 ± 0.03; CB: 0.89 ± 0.03 for both; P < 0.01). In the CB group at follow-up, 24-h RQ was positively associated with fasting glucose (r = 0.66, P < 0.05), glucose area under the curve (AUC) (r = 0.51, P < 0.05), and insulin AUC (r = 0.52, P < 0.05) and inversely associated with insulin sensitivity (r = -0.51, P < 0.05). Conclusions: The macronutrient composition of breakfast affects substrate utilization throughout the day in older adults. The consumption of a high-fat, lower-carbohydrate breakfast may reduce the risk of metabolic disease. This trial was registered at www.clinicaltrials.gov as NCT03164200.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT): Recommendations from the Biological Domain.

BACKGROUND: The responses to behavioral, pharmacological, or surgical obesity treatments are highly individualized. The Accumulating Data to Optimally Predict obesity Treatment (ADOPT) project provides a framework for how obesity researchers, working collectively, can generate the evidence base needed to guide the development of tailored, and potentially more effective, strategies for obesity treatment. OBJECTIVES: The objective of the ADOPT biological domain subgroup is to create a list of high-priority biological measures for weight-loss studies that will advance the understanding of individual variability in response to adult obesity treatments. This list includes measures of body composition, energy homeostasis (energy intake and output), brain structure and function, and biomarkers, as well as biobanking procedures, which could feasibly be included in most, if not all, studies of obesity treatment. The recommended high-priority measures are selected to balance needs for sensitivity, specificity, and/or comprehensiveness with feasibility to achieve a commonality of usage and increase the breadth and impact of obesity research. SIGNIFICANCE: The accumulation of data on key biological factors, along with behavioral, psychosocial, and environmental factors, can generate a more precise description of the interplay and synergy among them and their impact on treatment responses, which can ultimately inform the design and delivery of effective, tailored obesity treatments.

Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.

PURPOSE: Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity. CONCLUSIONS: Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

Decreased eating frequency linked to increased visceral adipose tissue, body fat, and BMI in Hispanic college freshmen.

BACKGROUND: To investigate the relationship between eating frequency and specific adiposity markers in a potentially high-risk and understudied population of Hispanic college freshmen. METHODS: This study included 92 Hispanic college freshmen (18-19 y). The following cross-sectional data were collected: height, weight, waist circumference, body mass index (BMI), dietary intake, body composition, physical activity, hepatic fat, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). RESULTS: Infrequent eaters ate 44% less often (2.5 ± 0.2 vs. 4.5 ± 0.8, p ≤ 0.01) and consumed 27% more calories per EO (p ≤ 0.01), while consuming 21% less kcals per day (p ≤ 0.01) compared to frequent eaters. Infrequent eaters had 8% higher BMIs (24.8 ± 4.4 vs. 22.9 ± 3.2 kg/m2) (p = 0.02), 60% higher BMI z-scores (0.5 ± 1.0 vs. 0.2 ± 1.0, p = 0.03), 21% higher VAT (298.3 ± 153.8 vs. 236.8 ± 78.2 ml, p = 0.03), 26% higher SAT (1150.1 ± 765.4 vs. 855.6 ± 494.6 ml, p = 0.03), and 8% higher total body fat (27.6 ± 10.8 vs. 25.3 ± 8.8%, p = 0.04) compared to frequent eaters while showing no significant difference in physical activity. These findings seem to be driven by females more than males. CONCLUSIONS: These findings suggest that infrequent eating is related to increased adiposity in Hispanic college freshmen, despite a decreased daily energy intake and no significant differences in physical activity. Yet, more research is needed to understand the underlying mechanisms of these findings, as well as investigate any potential causal relationship between eating frequency and adiposity in Hispanic youth.

Rationale, design, and baseline findings from HIPP: A randomized controlled trial testing a home-based, individually-tailored physical activity print intervention for African American women in the Deep South.

African American women report high rates of physical inactivity and related health disparities. In our previous formative research, we conducted a series of qualitative assessments to examine physical activity barriers and intervention preferences among African American women in the Deep South. These data were used to inform a 12-month Home-based, Individually-tailored Physical activity Print (HIPP) intervention, which is currently being evaluated against a wellness contact control condition among 84 post-menopausal African American women residing in the metropolitan area of Birmingham, Alabama. This paper reports the rationale, design and baseline findings of the HIPP trial. The accrued participants had an average age of 57 (SD=4.7), a BMI of 32.1 kg/m(2) (SD=5.16) with more than half (55%) having a college education and an annual household income under $50,000 (53.6%). At baseline, participants reported an average of 41.5 min/week (SD=49.7) of moderate intensity physical activity, and 94.1% were in the contemplation or preparation stages of readiness for physical activity. While social support for exercise from friends and family was low, baseline levels of self-efficacy, cognitive and behavioral processes of change, decisional balance, outcome expectations, and enjoyment appeared promising. Baseline data indicated high rates of obesity and low levels of physical activity, providing strong evidence of need for intervention. Moreover, scores on psychosocial measures suggested that such efforts may be well received. This line of research in technology-based approaches for promoting physical activity in African American women in the Deep South has great potential to address health disparities and impact public health.

NIH working group report-using genomic information to guide weight management: From universal to precision treatment.

OBJECTIVE: Precision medicine utilizes genomic and other data to optimize and personalize treatment. Although more than 2,500 genetic tests are currently available, largely for extreme and/or rare phenotypes, the question remains whether this approach can be used for the treatment of common, complex conditions like obesity, inflammation, and insulin resistance, which underlie a host of metabolic diseases. METHODS: This review, developed from a Trans-NIH Conference titled "Genes, Behaviors, and Response to Weight Loss Interventions," provides an overview of the state of genetic and genomic research in the area of weight change and identifies key areas for future research. RESULTS: Although many loci have been identified that are associated with cross-sectional measures of obesity/body size, relatively little is known regarding the genes/loci that influence dynamic measures of weight change over time. Although successful short-term weight loss has been achieved using many different strategies, sustainable weight loss has proven elusive for many, and there are important gaps in our understanding of energy balance regulation. CONCLUSIONS: Elucidating the molecular basis of variability in weight change has the potential to improve treatment outcomes and inform innovative approaches that can simultaneously take into account information from genomic and other sources in devising individualized treatment plans.

Physical activity monitoring in extremely obese adolescents from the Teen-LABORATORIES study.

BACKGROUND: The accuracy of physical activity (PA) monitors to discriminate between PA, sedentary behavior, and nonwear in extremely obese (EO) adolescents is unknown. METHODS: Twenty-five subjects (9 male/16 female; age = 16.5 ± 2.0 y; BMI = 51 ± 8 kg/m2) wore 3 activity monitors (StepWatch [SAM], Actical [AC], Actiheart [AH]) during a 400-m walk test (400MWT), 2 standardized PA bouts of varying duration, and 1 sedentary bout. RESULTS: For the 400MWT, percent error between observed and monitor-recorded steps was 5.5 ± 7.1% and 82.1 ± 38.6% for the SAM and AC steps, respectively (observed vs. SAM steps: -17.2 ± 22.2 steps; observed vs. AC steps: -264.5 ± 124.8 steps). All activity monitors were able to differentiate between PA and sedentary bouts, but only SAM steps and AH heart rate were significantly different between sedentary behavior and nonwear (P < .001). For all monitors, sedentary behavior was characterized by bouts of zero steps/counts punctuated by intermittent activity steps/counts; nonwear was represented almost exclusively by zero steps/counts. CONCLUSION: Of all monitors tested, the SAM was most accurate in terms of counting steps and differentiating levels of PA and thus, most appropriate for EO adolescents. The ability to accurately characterize PA intensity in EO adolescents critically depends on activity monitor selection.

Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart.

Circadian clocks are cell autonomous, transcriptionally based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are 2 transcription factors, CLOCK and BMAL1. The purpose of the present study was to reveal novel physiologic functions of BMAL1 in the heart, as well as to determine the pathologic consequences of chronic disruption of this circadian clock component. To address this goal, we generated cardiomyocyte-specific Bmal1 knockout (CBK) mice. Following validation of the CBK model, combined microarray and in silico analyses were performed, identifying 19 putative direct BMAL1 target genes, which included a number of metabolic (e.g., ß-hydroxybutyrate dehydrogenase 1 [Bdh1]) and signaling (e.g., the p85α regulatory subunit of phosphatidylinositol 3-kinase [Pik3r1]) genes. Results from subsequent validation studies were consistent with regulation of Bdh1 and Pik3r1 by BMAL1, with predicted impairments in ketone body metabolism and signaling observed in CBK hearts. Furthermore, CBK hearts exhibited depressed glucose utilization, as well as a differential response to a physiologic metabolic stress (i.e., fasting). Consistent with BMAL1 influencing critical functions in the heart, echocardiographic, gravimetric, histologic, and molecular analyses revealed age-onset development of dilated cardiomyopathy in CBK mice, which was associated with a severe reduction in life span. Collectively, our studies reveal that BMAL1 influences metabolism, signaling, and contractile function of the heart.

Comparative analyses of lung transcriptomes in patients with alveolar capillary dysplasia with misalignment of pulmonary veins and in foxf1 heterozygous knockout mice.

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a developmental disorder of the lungs, primarily affecting their vasculature. FOXF1 haploinsufficiency due to heterozygous genomic deletions and point mutations have been reported in most patients with ACDMPV. The majority of mice with heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence of pulmonary hemorrhage in some of them. By comparing transcriptomes of human ACDMPV lungs with control lungs using expression arrays, we found that several genes and pathways involved in lung development, angiogenesis, and in pulmonary hypertension development, were deregulated. Similar transcriptional changes were found in lungs of the postnatal day 0.5 Foxf1+/- mice when compared to their wildtype littermate controls; 14 genes, COL15A1, COL18A1, COL6A2, ESM1, FSCN1, GRINA, IGFBP3, IL1B, MALL, NOS3, RASL11B, MATN2, PRKCDBP, and SIRPA, were found common to both ACDMPV and Foxf1 heterozygous lungs. Our results advance knowledge toward understanding of the molecular mechanism of ACDMPV, lung development, and its vasculature pathology. These data may also be useful for understanding etiologies of other lung disorders, e.g. pulmonary hypertension, bronchopulmonary dysplasia, or cancer.

Understanding circadian gene function: animal models of tissue-specific circadian disruption.

Circadian rhythms are the daily patterns that occur within an organism, from gene expression to behavior. These rhythms are governed not only externally by environmental cues but also internally, with cell-autonomous molecular clock mechanisms present nearly ubiquitously throughout the cells of organisms. In more complex organisms, it has been suggested that the clock mechanisms serve varied functions depending on the tissue in which they are found. By disrupting core circadian gene function in specific tissues of animal models, the various roles of the circadian clock in differing tissues can begin to be defined. This review provides an overview of the model organisms used to elucidate tissue-specific functions of the molecular circadian clock.

Exercise dose, exercise adherence, and associated health outcomes in the TIGER study.

PURPOSE: To effectively evaluate activity-based interventions for weight management and disease risk reduction, objective and accurate measures of exercise dose are needed. This study examined cumulative exercise exposure defined by HR-based intensity, duration, and frequency as a measure of compliance with a prescribed exercise program and a predictor of health outcomes. METHODS: One thousand one-hundred fifty adults (21.3 ± 2.7 yr) completed a 15-wk exercise protocol consisting of 30 min·d, 3 d·wk, at 65%-85% maximum HR reserve. Computerized HR monitor data were recorded at every exercise session (33,473 valid sessions). To quantify total exercise dose, duration for each session was adjusted for average exercise intensity (%HR reserve) to create a measure of intensity minutes for each workout, which were summed over all exercise sessions to formulate an HR physical activity score (HRPAS). Regression analysis was used to examine the relation between HRPAS and physiological responses to exercise training. Compliance with the exercise protocol based on achievement of the minimum prescribed HRPAS was compared with adherence defined by attendance. RESULTS: On the basis of HRPAS, 868 participants were empirically defined as compliant, and 282 were noncompliant. HRPAS-based and attendance-based classifications of compliance and adherence differed in approximately 9% of participants. Higher HRPAS was associated with significant positive changes in body mass (P < 0.001), body mass index (P < 0.001), waist and hip circumferences (P < 0.001), percent body fat (P < 0.001), systolic blood pressure (P < 0.011), resting HR (P < 0.003), fasting glucose (P < 0.001), and total cholesterol (P < 0.02). Attendance-based adherence was associated with body mass, hip circumference, percent body fat, resting HR, and cholesterol (P < 0.05). CONCLUSIONS: The HRPAS is a quantifiable measure of exercise dose associated with improvement in health indicators beyond that observed when adherence is defined as session attendance.