BackgroundGuidelines recommend exercise for cardiovascular health, although evidence from trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. We performed a meta-analysis of randomized controlled trials to quantify the impact of exercise on cardiorespiratory fitness and a variety of conventional and novel cardiometabolic biomarkers in adults without cardiovascular disease.Methods and ResultsTwo researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random-effects meta-analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high-density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment–insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin-18 and lower levels of leptin, fibrinogen, and angiotensin II. In addition, we found that the exercise effects were modified by age, sex, and health status such that people aged <50 years, men, and people with type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome appeared to benefit more.ConclusionsThis meta-analysis showed that exercise significantly improved cardiorespiratory fitness and some cardiometabolic biomarkers. The effects of exercise were modified by age, sex, and health status. Findings from this study have significant implications for future design of targeted lifestyle interventions.

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

Background: Cocoa flavanols may improve cardiometabolic health. Evidence from small short-term randomized clinical

Purpose Patients with sickle cell disease (SCD) may experience sickle cell-related pain crises, also referred to as vaso-occlusive crises (VOCs), which are a substantial cause of morbidity and mortality. The study explored how VOC frequency and severity impacts health-related quality of life (HRQoL) and work productivity. Methods Three hundred and three adults with SCD who completed an online survey were included in the analysis. Patients answered questions regarding their experience with SCD and VOCs, and completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) and the Workplace Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP). Differences in ASCQ-Me and WPAI:SHP domains were assessed according to VOC frequency and severity. Results Nearly half of the patient sample (47.2%) experienced ≥ 4 VOCs in the past 12 months. The most commonly reported barriers to receiving care for SCD included discrimination by or trouble trusting healthcare professionals (39.6%, 33.3%, respectively), limited access to treatment centers (38.9%), and difficulty affording services (29.4%). Patients with more frequent VOCs reported greater impacts on emotion, social functioning, stiffness, sleep and pain, and greater absenteeism, overall productivity loss, and activity impairment than patients with less frequent VOCs (P < 0.05). Significant impacts on HRQoL and work productivity were also observed when stratifying by VOC severity (P < 0.05 for all ASCQ-Me and WPAI domains, except for presenteeism). Conclusions Results from the survey indicated that patients with SCD who had more frequent or severe VOCs experienced deficits in multiple domains of HRQoL and work productivity. Future research should examine the longitudinal relationship between these outcomes.

Sucrose nonfermenting-related kinase (SNRK) is a member of the AMPK-related kinase family, and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white adipose tissue (WAT) and brown adipose tissue (BAT), but SNRK expression diminishes in adipose tissue in obesity. In this study we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival; SNRK globally deficient pups die within 24 h after birth. Heterozygous mice are characterized by inflamed WAT and less BAT. Adipocyte-specific ablation of SNRK causes inflammation in WAT, ectopic lipid deposition in liver and muscle, and impaired adaptive thermogenesis in BAT. These metabolic disorders subsequently lead to decreased energy expenditure, higher body weight, and insulin resistance. We further confirm the significant association of common variants of the gene with obesity risk in humans. Through applying a phosphoproteomic approach, we identified eukaryotic elongation factor 1δ and histone deacetylase 1/2 as potential SNRK substrates. Taking these data together, we conclude that SNRK represses WAT inflammation and is essential to maintain BAT thermogenesis, making it a novel therapeutic target for treating obesity and associated metabolic disorders.

Our data indicate that the NPY rs16147 genotypes affect the change in abdominal adiposity in response to dietary interventions, and the effects of the rs16147 single-nucleotide polymorphism on central obesity and abdominal fat distribution were modified by dietary fat.

To our knowledge, our analysis is the first to comprehensively investigate the genomewide signals for LTPA in multiple ethnicities. These findings support the notion that genetic predisposition plays a critical role in determining LTPA, of which the biological and clinical implications warrants further investigation.

BackgroundAlthough increasing effort has been devoted to the promotion of a healthy lifestyle such as leisure time physical activity for cardio‐metabolic health, specific evidence supporting health policy remains sparse, particularly in those ethnically diverse populations where cardio‐metabolic diseases are reaching epidemic proportion and yet are grossly understudied.Methods and ResultsWe conducted a cross‐sectional analysis of the baseline data from 10 585 participants aged 35 to 74 free of cardiovascular diseases in the Brazilian Longitudinal Study of Adult Health. Leisure time physical activity status was defined by the American Heart Association and the World Health Organization recommendations (≥150 min/week moderate activities or 75 min/week vigorous activities). In total, 1183 (21%) women and 1387 (29%) men were active. After accounting for covariates, the favorable effects of leisure time physical activity on cardio‐metabolic parameters were evident. Specifically, the average blood pressure, heart rate, and Framingham Risk Score for cardiovascular diseases of the active were significantly lower within each sex. The ORs comparing the active versus the inactive women were 0.78 (95% CI: 0.66–0.92) for hypertension and 0.78 (95% CI: 0.65–0.93) for cardiovascular diseases in 10 years. Among men, the ORs were 0.75 (95% CI: 0.65–0.87) for hypertension and 0.73 (95% CI: 0.61–0.87) for diabetes. The 10‐year risk of cardiovascular diseases was significantly lower among the active men with a 33% reduction (OR=0.67, 95% CI: 0.57–0.78).ConclusionsWe observed beneficial effects of leisure time physical activity on cardio‐metabolic health in this large Brazilian population that are consistent with studies in North America and Europe.