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Background. Annual vaccination is the primary means for preventing influenza. However, great interindividual variability exists in vaccine responses, the cellular events that take place in vivo after vaccination are poorly understood, and appropriate biomarkers for vaccine responsiveness have not been developed.Methods. We immunized a cohort of healthy male adults with a licensed trivalent influenza vaccine and performed a timed assessment of global gene expression before and after vaccination. We analyzed the relationship between gene expression patterns and the humoral immune response to vaccination.Results. Marked up regulation of expression of genes involved in interferon signaling, positive IL-6 regulation, and antigen processing and presentation, were detected within 24 hours of immunization. The late vaccine response showed a transcriptional pattern suggestive of increased protein biosynthesis and cellular proliferation. Integrative analyses revealed a 494-gene expression signature—including STAT1, CD74, and E2F2—which strongly correlates with the magnitude of the antibody response. High vaccine responder status correlates with increased early expression of interferon signaling and antigen processing and presentation genes.Conclusions. The results highlight the role of a systems biology approach in understanding the molecular events that take place in vivo after influenza vaccination and in the development of better predictors of vaccine responsiveness. [ABSTRACT FROM PUBLISHER]

Thoracic aortic aneurysms and dissections (TAAD) cause significant morbidity and mortality, but the genetic origins of TAAD remain largely unknown. In a genome-wide analysis of 418 sporadic TAAD cases, we identified 47 copy number variant (CNV) regions that were enriched in or unique to TAAD patients compared to population controls. Gene ontology, expression profiling, and network analysis showed that genes within TAAD CNVs regulate smooth muscle cell adhesion or contractility and interact with the smooth muscle-specific isoforms of α-actin and β-myosin, which are known to cause familial TAAD when altered. Enrichment of these gene functions in rare CNVs was replicated in independent cohorts with sporadic TAAD (STAAD, n = 387) and inherited TAAD (FTAAD, n = 88). The overall prevalence of rare CNVs (23%) was significantly increased in FTAAD compared with STAAD patients (Fisher''s exact test, p = 0.03). Our findings suggest that rare CNVs disrupting smooth muscle adhesion or contraction contribute to both sporadic and familial disease. [Copyright &y& Elsevier]

Maintenance of circadian alignment between an organism and its environment is essential to ensure metabolic homeostasis. Synchrony is achieved by cell autonomous circadian clocks. Despite a growing appreciation of the integral relation between clocks and metabolism, little is known regarding the direct influence of a peripheral clock on cellular responses to fatty acids. To address this important issue, we utilized a genetic model of disrupted clock function specifically in cardiomyocytes in vivo (termed cardiomyocyte clock mutant (CCM)). CCM mice exhibited altered myocardial response to chronic high fat feeding at the levels of the transcriptome and lipidome as well as metabolic fluxes, providing evidence that the cardiomyocyte clock regulates myocardial triglyceride metabolism. Time-of-day-dependent oscillations in myocardial triglyceride levels, net triglyceride synthesis, and lipolysis were markedly attenuated in CCM hearts. Analysis of key proteins influencing triglyceride turnover suggest that the cardiomyocyte clock mactivates hormone-sensitive lipase during the active/awake phase both at transcriptional and post-translational (via AMP-activated protein kinase) levels. Consistent with increased net triglyceride synthesis during the end of the active/awake phase, high fat feeding at this time resulted in marked cardiac steatosis. These data provide evidence for direct regulation of triglyceride turnover by a peripheral clock and reveal a potential mechanistic explanation for accelerated metabolic pathologies after prevalent circadian misalignment in Western society. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion, peripheral insulin resistance, and increased hepatic glucose production. Genes that contribute to genetic susceptibility to T2DM function in numerous biochemical pathways. Uncoupling protein-2 ( UCP2) functions as a negative regulator of insulin secretion. Animal studies show induction of UCP2 plays a pathogenic role in the progression of obesity-induced T2DM and some human studies have shown an association between a common UCP2 polymorphism, Ala55Val (rs660339), and T2DM, obesity, and resting metabolic rate with the Val/Val genotype conferring increased risk. We investigated the relationship between the Ala55Val variant and incidence of T2DM among 12,056 participants in the Atherosclerosis Risk in Communities (ARIC) Study aged 45–64 years at baseline. Incident T2DM ( n = 1,406) cases were identified over 9 years of follow-up. The Val55 allele frequency was 44% in blacks and 41% in whites. The rate of T2DM per 1,000 person was 15.0, 15.6, and 15.6 yearsfor Ala/Ala, Ala/Val, and Val/Val genotypes, respectively. We found no significant association between UCP2 genotypes and incident T2DM in the whole cohort, in race-gender subgroups, or in categories of body mass index (normal, overweight and obese). The Ala55Val polymorphism of UCP2 was not associated with incident T2DM in the ARIC cohort. [ABSTRACT FROM AUTHOR]

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from mate Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM. and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H2O afterload), hearts were challenged with increased workload ( 140 cm H2O afterload plus 1 μM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase, Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability. [ABSTRACT FROM AUTHOR]

Cells/organs must respond both rapidly and appropriately to increased fatty acid availability; failure to do so is associated with the development of skeletal muscle and hepatic insulin resistance, pancreatic β-cell dysfunction, and myocardial contractile dysfunction. Here we tested the hypothesis that the intrinsic circadian clock within the cardiomyocytes of the heart allows rapid and appropriate adaptation of this organ to fatty acids by investigating the following: 1) whether circadian rhythms in fatty acid responsiveness persist in isolated adult rat cardiomyocytes, and 2) whether manipulation of the circadian clock within the heart, either through light/dark (L/D) cycle or genetic disruptions, impairs responsiveness of the heart to fasting in vivo. We report that both the intramyocellular circadian clock and diurnal variations in fatty acid responsiveness observed in the intact rat heart in vivo persist in adult rat cardiomyocytes. Reversal of the 12-h/12-h L/D cycle was associated with a re-entrainment of the circadian clock within the rat heart, which required 5- 8 days for completion. Fasting rats resulted in the induction of fatty acid-responsive genes, an effect that was dramatically attenuated 2 days after L/D cycle reversal. Similarly, a targeted disruption of the circadian clock within the heart, through overexpression of a dominant negative CLOCK mutant, severely attenuated induction of myocardial fatty acid-responsive genes during fasting. These studies expose a causal relationship between the circadian clock within the cardiomyocyte with responsiveness of the heart to fatty acids and myocardial triglyceride metabolism. [ABSTRACT FROM AUTHOR]

Purpose: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. Design: Population-based cross-sectional study. Methods: We studied 1,398 people aged 49 to 73 years with diabetes selected from four United States communities. We performed retinal photography on one randomly selected eye and graded for the presence and severity of diabetic retinopathy using a modification of the Early Treatment Diabetic Retinopathy Study scale. We performed genotyping of common polymorphic APOE alleles using polymerase chain reaction on genomic DNA from venous blood leukocytes. Results: The prevalence of diabetic retinopathy and hard exudates was 15.0% and 5.3% in Caucasians (n = 935), and 24.6% and 9.7% in African-Americans (n = 463), with type 2 diabetes. APOE gene polymorphisms were not associated with diabetic retinopathy in either Caucasians or African-Americans. In African-Americans, the ϵ2/ϵ4 genotype (n = 6) was associated with increased prevalence of hard exudates (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.30 to 12.90), as was the ϵ2/ϵ3 genotype (n = 9, OR 2.64, 95% CI 1.01 to 6.95). No association between APOE genotypes and hard exudates was found in Caucasians. Conclusions: These data suggest that APOE gene polymorphisms are not associated with diabetic retinopathy in either Caucasians or African-Americans with type 2 diabetes. [Copyright &y& Elsevier]

Objective: To examine the association between the apolipoprotein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. Design: Population-based cross-sectional study. Participants: Participants from the Atherosclerosis Risk in Communities Study (n = 10139; age range, 49–73 years). Methods: Retinal photography was performed on 1 randomly selected eye, and grading for presence of ARM was carried out using a modification of the Wisconsin ARM Grading System. Early ARM was defined as the presence of either soft drusen alone, retinal pigment epithelial depigmentation alone, or a combination of soft drusen with increased retinal pigment and/or depigmentation. DNA extracted from blood samples of participants were analyzed for common allelic variants of the APOE gene (ϵ2, ϵ3, and ϵ4). Main Outcome Measures: Presence of early ARM on retinal photographs. Results: The prevalence of early ARM was similar in participants with different APOE genotypes: ϵ2/ϵ2 (5.9%), ϵ2/ϵ3 (5.2%), ϵ2/ϵ4 (3.2%), ϵ3/ϵ3 (5.2%), ϵ3/ϵ4 (4.9%), and ϵ4/ϵ4 (4.1%). After controlling for age, gender, race, cigarette smoking, and other factors, early ARM was not associated with APOE genotypes, with an odds ratio (OR) of 1.35 (95% confidence interval [CI], 0.54–3.38) for ϵ2/ϵ2 genotype, an OR of 1.06 (95% CI, 0.80–1.40) for ϵ2/ϵ3 genotype, an OR of 0.63 (95% CI, 0.32–1.24) for ϵ2/ϵ4 genotype, an OR of 0.99 (95% CI, 0.80–1.24) for ϵ3/ϵ4 genotype, and an OR of 0.88 (95% CI, 0.47–1.63) for ϵ4/ϵ4 genotype, as compared with ϵ3/ϵ3 genotype (reference). No associations were found for specific early ARM signs or in analyses stratified by age, gender, race, or cigarette smoking status. Conclusions: These data provide no evidence of a strong association between the APOE gene and early ARM in middle-aged persons. This suggests that APOE is not likely a major determinant of the early stages of ARM in younger people. However, our study does not exclude the possibility of a weaker association or that APOE may influence only the development of late ARM in older populations, as reported in other studies. [Copyright &y& Elsevier]

Circadian clocks are intracellular molecular mechanisms that allow the cell to anticipate the time of day. We have previously reported that the intact rat heart expresses the major components of the circadian clock, of which its rhythmic expression in vivo is consistent with the operation of a fully functional clock mechanism. The present study exposes oscillations of circadian clock genes [brain and arylhydrocarbon receptor nuclear translocator-like protein 1 (bmal1), reverse strand of the c-erbaα gene (rev-erbaα), period 2 (per2), albumin D-element binding protein (dbp)] for isolated adult rat cardiomyocytes in culture. Acute (2 h) and/or chronic (continuous) treatment of cardiomyocytes with FCS (50% and 2.5%, respectively) results in rhythmic expression of circadian clock genes with periodicities of 20-24 h. In contrast, cardiomyocytes cultured in the absence of serum exhibit dramatically dampened oscillations in bmal1 and dbp only. Zeitgebers (timekeepers) are factors that influence the timing of the circadian clock. Glucose, which has been previously shown to reactivate circadian clock gene oscillations in fibroblasts, has no effect on the expression of circadian clock genes in adult rat cardiomyocytes, either in the absence or presence of serum. Exposure of adult rat cardiomyocytes to the sympathetic neurotransmitter norephinephrine (10 µM) for 2 h reinitiates rhythmic expression of circadian clock genes in a serumin-dependent manner. Oscillations in circadian clock genes were associated with 24-h oscillations in the metabolic genes pyruvate dehydrogenase kinase 4 (pdk4) and uncoupling protein 3 (ucp3). In conclusion, these data suggest that the circadian clock operates within the myocytes of the heart and that this molecular mechanism persists under standard cell culture conditions (i.e., 2.5% serum). Furthermore, our data suggest that norepinephrine, unlike glucose, influences the timing of the circadian clock within the heart and that the circadian clock may be a novel mechanism regulating myocardial metabolism. [ABSTRACT FROM AUTHOR]

Context Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the ε2 allele increasing and the ε4 allele decreasing risk. APOE allelic associations with chronic kidney disease beyond diabetic nephropathy are unknown, with no studies reported in high-risk African American populations. Objective To quantify the risk of chronic kidney disease progression associated with APOE in a population-based study including white, African American, diabetic, and nondiabetic individuals. Design, Setting, and Participants Prospective follow-up (through January 1, 2003) of Atherosclerosis Risk in Communities (ARIC) study participants, including 3859 African American and 10 661 white adults aged 45 to 64 years without severe renal dysfunction at baseline in 1987-1989, sampled from 4 US communities. Main Outcome Measures Incident chronic kidney disease progression, defined as hospitalization or death with kidney disease or increase in serum creatinine level of 0.4 mg/dL (35 μmol/L) or more above baseline, examined by APOE genotypes and alleles. Results During median follow-up of 14 years, chronic kidney disease progression developed in 1060 individuals (incidence per 1000 person-years: 5.5 overall; 8.8 in African Americans and 4.4 in whites). Adjusting for major chronic kidney disease risk factors, ε2 moderately increased and ε4 decreased risk of disease progression (likelihood ratio test, P = .03). Further adjustment for low- and high-density lipoprotein cholesterol and triglycerides did not attenuate relative risks (RRs) (ε2: 1.08 [95% CI, 0.93-1.25] and ε4: 0.85 [95% CI, 0.75-0.95] compared with ε3; likelihood ratio test, P = .008). ε4 decreased risk of end-stage renal disease (RR, 0.60 [95% CI, 0.43-0.84]). ε2 was associated with a decline in renal function (RR, 1.25 [95% CI, 1.02-1.53]), though not with events, such as hospitalizations or end-stage renal disease. Risks were similar stratified by race, sex, diabetes, and hypertension (all P values for interaction >.05). Excess risk of chronic kidney disease in African Americans was not explained by APOE alleles. Conclusions APOE variation predicts chronic kidney disease progression, independent of diabetes, race, lipid, and nonlipid risk factors. Our study suggests that nonlipid-mediated pathways, such as cellular mechanisms of kidney remodeling, may be involved in the association of APOE alleles and progression of chronic kidney disease. [ABSTRACT FROM AUTHOR]

Cardiac and skeletal muscle both respond to elevated fatty acid availability by increasing fatty acid oxidation, an effect mediated in large part by peroxisome proliferator-activated receptor-α (PPARα). We hypothesized that cardiac and skeletal muscle alter their responsiveness to fatty acids over the course of the day, allowing optimal adaptation when availability of this substrate increases. In the current study, pyruvate dehydrogenase kinase 4 (pdk4) was utilized as a representative PPARα-regulated gene. Opposing diurnal variations in pdk4 expression were observed in cardiac and skeletal muscle isolated from the ad libitum-fed rat; pdk4 expression peaked in the middle of the dark and light phases, respectively. Elevation of circulating fatty acid levels by high-fat feeding, fasting, and streptozotocin-induced diabetes increased pdk4 expression in both heart and soleus muscle. Highest levels of induction were observed during the dark phase, regardless of muscle type or intervention. Specific activation of PPARα with WY-14643 rapidly induced pdk4 expression in heart and soleus muscle. Highest levels of induction were again observed during the dark phase. The same pattern of induction was observed for the PPARα-regulated genes malonyl-CoA decarboxylase and uncoupling protein 3. Investigation into the potential mechanism(s) for these observations exposed a coordinated upregulation of transcriptional activators of the PPARα system during the night, with a concomitant downregulation of transcriptional repressors in both muscle types. In conclusion, responsiveness of cardiac and skeletal muscle to fatty acids exhibits a marked diurnal variation. These observations have important physiological and pathophysiological implications, ranging from experimental design to pharmacological treatment of patients. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 World Obesity Federation.)

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-study—Baseline 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.

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., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of interests M.S.B. is a member of the Advisory Board of Cell Metabolism. The authors have no other interests to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 (β: -0.0793; 95% credible interval: -0.1568, -0.0017) and snacking (β: -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 (β: 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 (β: -0.0023; 95% credible interval: -0.0042, -0.0004) and an increased preference for the prudent pattern (β: 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.

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.

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/m 2 ) ( 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., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2018.)

Objective: This study aimed to test experiential and behavioral processes of change as mediators of the prediction of exercise behavior by two self-regulation traits, self-efficacy and self-motivation, while controlling for exercise enjoyment., Methods: Structural equation modeling was applied to questionnaire responses obtained from a diverse sample of participants. Objective measures defined adherence (928 of 1,279 participants attended 80 % or more of sessions) and compliance (867 of 1,145 participants exercised 30 min or more each session at their prescribed heart rate)., Results: Prediction of attendance by self-efficacy (inversely) and self-motivation was direct and also indirect, mediated through positive relations with the typical use of behavioral change processes. Enjoyment and self-efficacy (inversely) predicted compliance with the exercise prescription., Conclusions: The results support the usefulness of self-regulatory behavioral processes of the transtheoretical model for predicting exercise adherence, but not compliance, extending the supportive evidence for self-regulation beyond self-reports of physical activity used in prior observational studies.

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.

Given that calcium metabolism is influenced by genes and is tightly linked to energy-utilizing pathways, this study evaluated the association of single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and calcium-sensing receptor (CASR) with resting energy expenditure (REE). In 273 boys and girls, 7-12 years of age, cross-sectional REE was measured via indirect calorimetry, body composition by DXA, and dietary measures by 24-h recall. SNPs for VDR Cdx-2 (rs11568820) and CASR A986S (rs1801725) were genotyped using the Illumina Golden Gate assay. Multiple linear regression models were used to determine the association between SNPs and REE. African American carriers of the 'A' VDR Cdx2 allele had increased levels of REE in the overall sample, and this association was apparent among participants with an adiposity level of <25 % and 30 % body fat in males and females, respectively. For CASR, an association between carriers of the 'A' allele and REE was observed only in those in the upper median of calcium intake. VDR and CASR variants are associated with REE in children and are influenced by levels of calcium intake and adiposity. Our results bring awareness to mechanisms underlying the regulation of REE and biological and dietary influential factors.

Aim: Neoplastic transformation provides one of the few existing opportunities to analyze molecular changes in real time during the initiation and progression of breast cancer., Materials & Methods: Human mammary epithelial cells underwent neoplastic reprogramming, generating one line of semitransformed, premalignant cells and two separate, temporal lines of fully transformed human mammary epithelial cells (THMECs). An Illumina Infinium HumanMethylation27 BeadChip was used to analyze DNA methylation alterations in 27,578 CpG loci at three consecutive time points over an 80-day (d) transformation period., Results: The mean β value for semitransformed human mammary epithelial cells CpG loci (0.245) was much greater than for either THMEC-40d (0.055) or THMEC-80d (0.066), indicating a large loss of methylation after neoplastic induction. In addition, 54% of CpG loci were hypermethylated during the THMEC-40d to THMEC-80d transition. We observed that the CpG loci exhibiting DNA methylation changes during early oncogenesis were enriched for biological functions like cellular movement; this was distinctly different than in the later, more progressive stages of the transformation process enriched for processes involving differentiation., Conclusion: The timing of major methylomic changes may be important in directing the cell toward a more cancerous phenotype. In addition, gene-specific hypermethylation appears to silence developmentally related genes, leading to dedifferentiation.

The development of obesity is the consequence of a multitude of complex interactions between both genetic and environmental factors. It has been suggested that the dramatic increase in the prevalence of obesity over the past 30 years has been the result of environmental changes that have enabled the full realization of genetic susceptibility present in the population. Among the many environmental alterations that have occurred in our recent history is the ever-increasing dyssynchrony between natural cycles of light/dark and altered patterns of sleep/wake and eating behavior associated with our "24-hour" lifestyle. An extensive research literature has established clear links between increased risk for obesity and both sleep deprivation and shift work, and our understanding of the consequences of such dyssynchrony at the molecular level is beginning to emerge. Studies linking alterations in cellular circadian clocks to metabolic dysfunction point to the increasing importance of chronobiology in obesity etiology.

The National Human Genome Research Institute recommends pursuing "genomic information to improve behavior change interventions" as part of its strategic vision for genomics. The limited effectiveness of current behavior change strategies may be explained, in part, by their insensitivity to individual variation in adherence responses. The first step in evaluating whether genomics can inform customization of behavioral recommendations is evidence reviews to identify adherence macrophenotypes common across behaviors and individuals that have genetic underpinnings. Conceptual models of how biological, psychological, and environmental factors influence adherence also are needed. Researchers could routinely collect biospecimens and standardized adherence measurements of intervention participants to enable understanding of genetic and environmental influences on adherence, to guide intervention customization and prospective comparative effectiveness studies.

Background/introduction: The purpose of this study was to examine the race/ethnicity bias of using waist circumference (WC) to estimate abdominal fat., Methods: A total of 771 females and 484 males (17-35 yr) were tested one to three times during a prescribed 30-wk aerobic exercise program. The race/ethnicity distribution for women was non-Hispanic white, 29%; Hispanic, 25%; African American (AA), 35%; Asian Indian, 3%; and Asian, 8%. The distribution for men was non-Hispanic white, 37%; Hispanic, 26%; AA, 22%; Asian Indian, 5%; and Asian, 10%. Abdominal fat (L1-L5) was estimated from whole-body scanning using dual-energy x-ray absorptiometry (DXA Abd-Fat)., Results: DXA Abd-Fat varied by race/ethnicity after accounting for WC and height in both women and men. The increase in DXA Abd-Fat per increase in WC was lower in the Asian and Asian-Indian women than that in the other women. The increase in DXA Abd-Fat per increase in WC was higher in the AA men and lower in the Asian-Indian men than that in the other men. These differential race/ethnicity effects were most notable when WC exceeded ≍90 cm in the women and ≍100 cm in the men, values which are consistent with current definitions of abdominal obesity in the United States., Conclusions: Prediction equations for abdominal fat using WC that do not account for race/ethnicity group provide biased estimates. These results may affect assessment of disease risk from abdominal obesity among racial/ethnic groups.

MicroRNAs (miRNAs) regulate cell physiology by altering protein expression, but the biology of platelet miRNAs is largely unexplored. We tested whether platelet miRNA levels were associated with platelet reactivity by genome-wide profiling using platelet RNA from 19 healthy subjects. We found that human platelets express 284 miRNAs. Unsupervised hierarchical clustering of miRNA profiles resulted in 2 groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed (DE) between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. Using whole genome mRNA expression data on these same subjects, we computationally generated a high-priority list of miRNA-mRNA pairs in which the DE platelet miRNAs had binding sites in 3'-untranslated regions of DE mRNAs, and the levels were negatively correlated. Three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5, and miR-107:CLOCK) were selected from this list, and all 3 miRNAs knocked down protein expression from the target mRNA. Reduced activation from platelets lacking PRKAR2B supported these findings. In summary, (1) platelet miRNAs are able to repress expression of platelet proteins, (2) miRNA profiles are associated with and may predict platelet reactivity, and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets.

Molecular, cellular, and animal-based studies have recently exposed circadian clocks as critical regulators of energy balance. Invariably, mouse models of genetically manipulated circadian clock components display features indicative of altered lipid/fatty acid metabolism, including differential adiposity and circulating lipids. The purpose of this minireview is to provide a comprehensive summary of current knowledge regarding the regulation of fatty acid metabolism by distinct cell autonomous circadian clocks. The implications of these recent findings for cardiometabolic disease and human health are discussed.

Purpose: Popular generalized equations for estimating percent body fat (BF%) developed with cross-sectional data are biased when applied to racially/ethnically diverse populations. We developed accurate anthropometric models to estimate dual-energy x-ray absorptiometry BF% (DXA-BF%) that can be generalized to ethnically diverse young adults in both cross-sectional and longitudinal field settings., Methods: This longitudinal study enrolled 705 women and 428 men (aged 17-35 yr) for 30 wk of exercise training (3 d·wk(-1) for 30 min·d(-1) of 65%-85% predicted V˙O2max). The distribution of ethnicity was as follows: 37% non-Hispanic white, 29% Hispanic, and 34% African-American. DXA-BF%, skinfold thicknesses, and body mass index (BMI) were collected at baseline and after 15 and 30 wk., Results: Skinfolds, BMI, and race/ethnicity were significant predictors of DXA-BF% in linear mixed model regression analysis. For comparable anthropometric measures (e.g., BMI), DXA-BF% was lower in African-American women and men but higher in Hispanic women compared with non-Hispanic white. Addition of BMI to the skinfold model improved the SEE for women (3.6% vs 4.0%), whereas BMI did not improve prediction accuracy of men (SEE = 3.1%)., Conclusions: These equations provide accurate predictions of DXA-BF% for diverse young women and men in both cross-sectional and longitudinal settings. To our knowledge, these are the first published body composition equations with generalizability to multiple time points, and the SEE estimates are among the lowest published in the literature.

Objective: To test the factorial validity and measurement equivalence/invariance of scales used to measure processes of change derived from the Transtheoretical Model (TTM) applied to physical activity., Methods: Confirmatory factor analysis of questionnaire responses obtained from a diverse sample (N = 1,429) of students enrolled in the Training Interventions and Genetics of Exercise Response (TIGER) Study at the University of Houston during academic years 2004-2005 through 2007-2008. Cohorts of students (N = 1,163) completed the scales at the beginning and end of each Fall semester, permitting longitudinal analysis., Results: Theoretically and statistically sound models were developed that support the factorial validity of nine of the ten hypothesized 1st-order factors. A structure of nine correlated 1st order factors or a hierarchical structure of those factors subordinate to two correlated 2nd-order factors were each defensible. Multi-group invariance of each model was confirmed across race/ethnicity groups (African American, Hispanic, non-Hispanic White), gender, age, BMI levels, employment status, physical activity level, and study adherence. Longitudinal invariance across the semester was also confirmed., Conclusion: The scores from the scales provide valid assessments that can be used in observational studies of naturally occurring change or in interventions designed to test the usefulness of TTM processes as mediators of change in physical activity among college students. Item content and factor structure require further evaluation in other samples in order to advance TTM theory applied to physical activity.

Impaired myocardial contractile function is a hallmark of heart failure (HF), which may present under resting conditions and/or during physiological stress. Previous studies have reported that high fat feeding in mild to moderate HF/left ventricular (LV) dysfunction is associated with improved contractile function at baseline. The goal of this study was to determine whether myocardial function is compromised in response to physiological stress and to evaluate the global gene expression profile of rats fed high dietary fat after infarction. Male Wistar rats underwent ligation or sham surgery and were fed normal chow (NC; 10% kcal fat; Sham + NC and HF + NC groups) or high-fat chow (SAT; 60% kcal saturated fat; Sham + SAT and HF + SAT groups) for 8 wk. Myocardial contractile function was assessed using a Millar pressure-volume conductance catheter at baseline and during inferior vena caval occlusions and dobutamine stress. Steady-state indexes of systolic function, LV +dP/dt(max), stroke work, and maximal power were increased in the HF + SAT group versus the HF + NC group and reduced in the HF + NC group versus the Sham + NC group. Preload recruitable measures of contractility were decreased in HF + NC group but not in the HF + SAT group. beta-Adrenergic responsiveness [change in LV +dP/dt(max) and change in cardiac output with dobutamine (0-10 microg x kg(-1) x min(-1))] was reduced in HF, but high fat feeding did not further impact the contractile reserve in HF. The contractile reserve was reduced by the high-fat diet in the Sham + SAT group. Microarray gene expression analysis revealed that the majority of significantly altered pathways identified contained multiple gene targets correspond to cell signaling pathways and energy metabolism. These findings suggest that high saturated fat improves myocardial function at rest and during physiological stress in infarcted hearts but may negatively impact the contractile reserve under nonpathological conditions. Furthermore, high fat feeding-induced alterations in gene expression related to energy metabolism and specific signaling pathways revealed promising targets through which high saturated fat potentially mediates cardioprotection in mild to moderate HF/LV dysfunction.

An annual review publication of the most significant articles in exercise, fitness, and performance genomics begins with this article, which covers 2 yr, 2008 and 2009. The review emphasizes the strongest articles as defined by sample size, quality of phenotype measurements, quality of the exercise program or physical activity exposure, study design, adjustment for multiple testing, quality of genotyping, and other related study characteristics. With this avowed focus on the highest quality articles, only a small number of published articles are reviewed. Among the most significant findings reported here are a brief overview of the first genome-wide association study of the genetic differences between exercisers and nonexercisers. In addition, the latest results on the actinin alpha 3 (ACTN3) R577X nonsense polymorphism are reviewed, emphasizing that no definitive conclusion can be reached at this time. Recent studies that have dealt with mitochondrial DNA haplogroups and endurance performance are described. Published reports indicating that physical activity may attenuate the effect of the fat mass and obesity associated (FTO) gene risk allele on body mass index are reviewed. Articles that have tested the contributions of specific genes to the response of glucose and insulin metabolism traits to regular exercise or physical activity level are considered and found to be generally inconclusive at this stage. Studies examining ethnic differences in the response of blood lipids and lipoproteins to exercise training cannot unequivocally relate these to apolipoprotein E (APOE) genotypes. Hemodynamic changes with exercise training were reported to be associated to sequence variation in kinesin heavy chain (KIF5B), but no replication study is available as of yet. We conclude from this first installment that exercise scientists need to prioritize high-quality research designs and that replication studies with large sample sizes are urgently needed.

Objective: The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise., Participants: A multiracial/ethnic cohort (N = 1,567; 39% male), age 18 to 35 years, participated in the study., Methods: Subjects underwent 30 weeks of exercise training, 3 days/week, for 40 minutes at 65% to 85% of age- and gender-predicted maximum heart rate reserve. Multiple measures of body size/composition, heart rate, and blood pressure were obtained., Results: A total of 1,567 participants, (39% male), age 18 to 35 years, participated in the TIGER study. The prevalence of overweight/obesity in participants was 48.0%/19.3% in non-Hispanic Whites, 55.3%/24.2% in Hispanic Whites, 54.9%/25.4% in African Americans, and 38.3%/11.3% in Asians. Average within-semester retention was 68%, but overall retention (30 weeks, 2 semesters) was 20%., Conclusions: The TIGER study represents an efficacious strategy for introducing college-aged individuals to regular aerobic exercise.

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 microM epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Circadian clocks are intracellular molecular mechanisms designed to allow the cell, organ, and organism to prepare for an anticipated stimulus prior to its onset. In order for circadian clocks to maintain their selective advantage, they must be entrained to the environment. Light, sound, temperature, physical activity (including sleep/wake transitions), and food intake are among the strongest environmental factors influencing mammalian circadian clocks. Normal circadian rhythmicities in these environmental factors have become severely disrupted in our modern day society, concomitant with increased incidence of type 2 diabetes mellitus, obesity, and cardiovascular disease. Here, we review our current knowledge regarding the roles of peripheral circadian clocks, concentrating on those found within tissues directly involved in metabolic homeostasis and cardiovascular function. We propose that both inter- and intra-organ dyssynchronization, through alteration/impairment of peripheral circadian clocks, accelerates the development of cardiovascular disease risk factors associated with cardiometabolic syndrome.