Chloroquine increases phosphorylation of AMPK and Akt in myotubes.

AIMS: There are reports that ataxia telangiectasia mutated (ATM) can activate the AMP-activated protein kinase (AMPK) and also Akt, two kinases that play integral parts in cardioprotection and metabolic function. We hypothesized that chloroquine and resveratrol, both known ATM activators, would also activate AMPK and Akt. MAIN METHODS: Phosphorylation of AMPK and Akt was assessed after C2C12 myotubes were exposed to chloroquine or resveratrol. Additional experiments were done in cells expressing shRNA against ATM or in the presence of the ATM inhibitor KU55933. The effects of chloroquine on intracellular calcium were assessed with the fluorescent probe Calcium Green-1 AM. KEY FINDINGS: 0.5 mM chloroquine increased AMPK phosphorylation by nearly 4-fold (P<0.05), and 0.25 mM chloroquine roughly doubled Akt phosphorylation (P<0.05). Chloroquine also increased autophosphorylation of ATM by ~50% (P<0.05). Resveratrol (0.15 mM) increased AMPK phosphorylation about three-fold (P<0.05) but in contrast to chloroquine sharply decreased Akt phosphorylation. Chloroquine increased AMPK and Akt phosphorylation in myotubes expressing shRNA against ATM that reduced ATM protein levels by about 90%. Likewise, chloroquine-stimulated phosphorylation of AMPK and Akt and resveratrol-stimulated phosphorylation of AMPK were not altered by inhibition of ATM. Chloroquine decreased intracellular calcium by >50% concomitant with a decrease in glucose transport. SIGNIFICANCE: These ATM-independent effects of chloroquine on AMPK and Akt and the additional effect to decrease intracellular calcium are likely to partially underlie the positive metabolic effects of chloroquine that have been reported in the literature.

Obesity and Aerobic Fitness among Urban Public School Students in Elementary, Middle, and High School.

AIMS AND OBJECTIVES: To assess the prevalence of cardiovascular disease risk among urban public school students through a collaborative school district and university partnership. METHODS: Children and adolescents in grades K-12 from 24 urban public schools participated in measurements of height, weight, and other health metrics during the 2009-2010 school year. Body mass index (BMI) percentiles and z-scores were computed for 4673 students. President's Challenge 1-mile endurance run was completed by 1075 students ages 9-19 years. Maximal oxygen consumption (⩒O2max) was predicted using an age-, sex-, and BMI-specific formula to determine health-related fitness. Resting blood pressure (BP) was assessed in 1467 students. Regression analyses were used to compare BMI z-scores, fitness, and age- and sex-specific BP percentiles across grade levels. Chi-square tests were used to explore the effect of sex and grade-level on health-related outcomes. RESULTS: Based on BMI, 19.8% were categorized as overweight and 24.4% were obese. Included in the obese category were 454 students (9.7% of sample) classified with severe obesity. Using FITNESSGRAM criteria, 50.2% of students did not achieve the Healthy Fitness Zone (HFZ); the proportion of students in the Needs Improvement categories increased from elementary to middle school to high school. Male students demonstrated higher fitness than female students, with 61.4% of boys and only 35.4% of girls meeting HFZ standards. Elevated BP was observed among 24% of 1467 students assessed. Systolic and diastolic BP z-scores revealed low correlation with BMI z-scores. CONCLUSIONS: A community-university collaboration identified obesity, severe obesity, overweight, and low aerobic fitness to be common risk factors among urban public school students.

Postprandial plasma incretin hormones in exercise-trained versus untrained subjects.

INTRODUCTION: After food ingestion, the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by the intestines into circulation where they act on the pancreas to promote insulin secretion. We evaluated the hypothesis that low postprandial plasma insulin levels in lean exercise-trained individuals are associated with low concentrations of incretin hormones. METHODS: A cross-sectional study was performed to compare postprandial incretin hormone levels in lean endurance exercise-trained individuals (EX; n = 14, ≥40 yr) and age- and sex-matched, nonobese, sedentary control subjects (CON, n = 14). The main outcome measures were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as measured in plasma samples collected during a 2-h,75-g oral glucose tolerance test (OGTT). RESULTS: The EX group had lower body fat percentage (14.6% ± 1.1% vs 23.3% ± 1.7%, P = 0.0002) and higher maximal oxygen uptake (53 ± 2 vs 34 ± 2, P < 0.0001) than CON. Glucose AUC did not differ between groups (P = 0.20). Insulin AUC was lower in EX (2.5 ± 0.5 vs 4.2 ± 1.2 µU·mL·1000 min, P = 0.02). No differences were observed between groups (EX and CON, respectively) for GLP-1 AUC (3.5 ± 0.7 vs 4.1 ± 1.1 pmol·min·100 L, P = 0.61) or GIP AUC (19.2 ± 1.4 vs 18.0 ± 1.4 pg·min·1000 mL; P = 0.56). In CON, insulin AUC was correlated with AUC for GLP-1 (r = 0.53, P = 0.05) and GIP (r = 0.71, P = 0.004), but no such correlations were observed in EX (both P ≥ 0.67). CONCLUSIONS: Low postprandial insulin levels in lean exercise-trained individuals are not attributable to lower incretin hormone concentrations. However, exercise may decrease the dependency of postprandial insulin levels on incretin hormones.

Exercise and cardiometabolic risk factors in graduate students: a longitudinal, observational study.

OBJECTIVE: To evaluate cardiometabolic risk of students longitudinally and compare them with age-matched national samples. PARTICIPANTS: Participants are 134 graduate students enrolled between August 2005 and May 2010. METHODS: Students were assessed at the beginning and end of their 3-year curriculum. Comparative samples included 966 National Health and Nutrition Examination Survey participants and 5,154 National College Health Assessment respondents. RESULTS: Most students had desirable weight, blood glucose, lipids, and fitness at both time points. However, 26.9% had elevated blood pressure, 29.9% performed aerobic exercise < 3 days/week, and 80.6% consumed < 5 fruits/vegetables daily. Relative to young adults nationwide, these students exhibited more favorable exercise patterns, dietary patterns, and cardiometabolic indices. Over time, increases in adiposity and decreases in exercise frequency correlated with adverse changes in lipid concentrations and fitness. CONCLUSIONS: Small changes in lifestyle behaviors and adiposity within a healthy cohort of young adults significantly influenced cardiometabolic indices during their graduate career.

Relationship of acetabular dysplasia and femoroacetabular impingement to hip osteoarthritis: a focused review.

Hip osteoarthritis (OA) leads to significant functional limitations and economic burden. If modifiable risk factors for hip OA are identified, it may be possible to implement preventative measures. Bony abnormalities associated with acetabular dysplasia (AD) and femoroacetabular impingement have been recently implicated as risk factors for hip OA. The purpose of this focused review is to summarize the available evidence describing the relationship between bony abnormalities and hip OA. A librarian-assisted database search with PubMed, Embase, and CENTRAL was performed. Relevant articles were identified and assessed for inclusion criteria. The authors reviewed cohort and case-control studies that reported on the association between abnormal hip morphology and hip OA. The available literature suggests that an association exists between bony abnormalities found in AD and femoroacetabular impingement and hip OA, and preliminary evidence suggests that AD is a risk factor for OA; however, these conclusions are based on limited evidence. Prospective, longitudinal studies are needed to confirm the causal relationship between abnormal hip morphology and the future development of hip OA.