Trends in Prevalence of Overweight and Obesity in Danish Infants,Children and Adolescents – Are We Still on a Plateau?

Background

After the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world.

Aim

To examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again.

Methods

The trends in the prevalence rates were based on three data sets providing comparable repeated estimates: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI).

Results

The prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI’s from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed.

Conclusion

This study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.     

SorLA Controls Neurotrophic Activity by Sorting of GDNF and Its Receptors GFRα1 and RET

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Highlights? SorLA is a sorting receptor for GDNF and its signaling receptors GFRa1 and RET ? The SorLA/GFRa1 complex targets GDNF for lysosomal degradation, while GFRa1 is recycled ? SorLA/GFRa1 targets RET for endocytosis and influences GDNF-induced neurotrophic effects ? SorLA knockout mice display altered dopaminergic function and an ADHD-like phenotype     

A high-throughput method for liquid chromatography–tandem mass spectrometry determination of plasma alkylresorcinols,biomarkers of whole grain wheat and rye intake

Plasma alkylresorcinols are increasingly analyzed in cohort studies to improve estimates of whole grain intake and their relationship with disease incidence. Current methods require large volumes of solvent (>10 ml/sample) and have relatively low daily sample throughput. We tested five different supported extraction methods for extracting alkylresorcinols from plasma and improved a normal-phase liquid chromatography coupled to a tandem mass spectrometer method to reduce sample analysis time. The method was validated and compared with gas chromatography–mass spectrometry analysis. Sample preparation with HybridSPE supported extraction was most effective for alkylresorcinol extraction, with recoveries of 77–82% from 100 μl of plasma. The use of 96-well plates allowed extraction of 160 samples per day. Using a 5-cm NH₂ column and heptane reduced run times to 3 min. The new method had a limit of detection and limit of quantification equivalent to 1.1–1.8 nmol/L and 3.5–6.1 nmol/L plasma, respectively, for the different alkylresorcinol homologues. Accuracy was 93–105%, and intra- and inter-batch precision values were 4–18% across different plasma concentrations. This method makes it possible to quantify plasma alkylresorcinols in 100 μl of plasma at a rate of at least 160 samples per day without the need for large volumes of organic solvents.     

Heregulin-induced epigenetic regulation of the utrophin-A promoter

Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.     

Cerebral carbohydrate cost of physical exertion in humans

Above a certain level of cerebral activation the brain increases its uptake of glucose more than that of O(2), i.e., the cerebral metabolic ratio of O(2)/(glucose + 12 lactate) decreases. This study quantified such surplus brain uptake of carbohydrate relative to O(2) in eight healthy males who performed exhaustive exercise. The arterial-venous differences over the brain for O(2), glucose, and lactate were integrated to calculate the surplus cerebral uptake of glucose equivalents. To evaluate whether the amount of glucose equivalents depends on the time to exhaustion, exercise was also performed with beta(1)-adrenergic blockade by metoprolol. Exhaustive exercise (24.8 +/- 6.1 min; mean +/- SE) decreased the cerebral metabolic ratio from a resting value of 5.6 +/- 0.2 to 3.0 +/- 0.4 (P < 0.05) and led to a surplus uptake of glucose equivalents of 9 +/- 2 mmol. beta(1)-blockade reduced the time to exhaustion (15.8 +/- 1.7 min; P < 0.05), whereas the cerebral metabolic ratio decreased to an equally low level (3.2 +/- 0.3) and the surplus uptake of glucose equivalents was not significantly different (7 +/- 1 mmol; P = 0.08). A time-dependent cerebral surplus uptake of carbohydrate was not substantiated and, consequently, exhaustive exercise involves a brain surplus carbohydrate uptake of a magnitude comparable with its glycogen content.     

Cerebral metabolism during upper and lower body exercise.

When continuation of exercise calls for a "will," the cerebral metabolic ratio of O2 to (glucose + lactate) decreases, with the largest reduction (30-50%) at exhaustion. Because a larger effort is required to exercise with the arms than with the legs, we tested the hypothesis that the reduction in the cerebral metabolic ratio would become more pronounced during arm cranking than during leg exercise. The cerebral arterial-venous differences for blood-gas variables, glucose, and lactate were evaluated in two groups of eight subjects during exhaustive arm cranking and leg exercise. During leg exercise, exhaustion was elicited after 25 +/- 6 (SE) min, and the cerebral metabolic ratio was reduced from 5.6 +/- 0.2 to 3.5 +/- 0.2 after 10 min and to 3.3 +/- 0.3 at exhaustion (P < 0.05). Arm cranking lasted for 35 +/- 4 min and likewise decreased the cerebral metabolic ratio after 10 min (from 6.7 +/- 0.4 to 5.0 +/- 0.3), but the nadir at exhaustion was only 4.7 +/- 0.4, i.e., higher than during leg exercise (P < 0.05). The results demonstrate that exercise decreases the cerebral metabolic ratio when a conscious effort is required, irrespective of the muscle groups engaged. However, the comparatively small reduction in the cerebral metabolic ratio during arm cranking suggests that it is influenced by the exercise paradigm.     

Array-A-Lizer: A serial DNA microarray quality analyzer

Background  

The proliferate nature of DNA microarray results have made it necessary to implement a uniform and quick quality control of experimental results to ensure the consistency of data across multiple experiments prior to actual data analysis.     

Association with membrane protrusions makes ErbB2 an internalization-resistant receptor

In contrast to the epidermal growth factor (EGF) receptor, ErbB2 is known to remain at the plasma membrane after ligand binding and dimerization. However, why ErbB2 is not efficiently down-regulated has remained elusive. Basically, two possibilities exist: ErbB2 is internalization resistant or it is efficiently recycled after internalization. By a combination of confocal microscopy, immunogold labeling electron microscopy, and biochemical techniques we show that ErbB2 is preferentially associated with membrane protrusions. Moreover, it is efficiently excluded from clathrin-coated pits and is not seen in transferrin receptor-containing endosomes. This pattern is not changed after binding of EGF, heregulin, or herceptin. The exclusion from coated pits is so pronounced that it cannot just be explained by lack of an internalization signal. Although ErbB2 is a raft-associated protein, the localization of ErbB2 to protrusions is not a result of raft binding. Also, an intact actin cytoskeleton is not required for keeping ErbB2 away from coated pits. However, after efficient cross-linking, ErbB2 is removed from protrusions to occur on the bulk membrane, in coated pits, and in endosomes. These data show that ErbB2 is a remarkably internalization-resistant receptor and suggest that the mechanism underlying the firm association of ErbB2 with protrusions also is the reason for this resistance.     

Functional consequences of alterations to Ile279, Ile283, Glu284, His285, Phe286, and His288 in the NH2-terminal part of transmembrane helix M3 of the Na+,K(+)-ATPase

Mutations Ile279 --> Ala, Ile283 --> Ala, Glu284 --> Ala, His285 --> Ala, His285 --> Lys, His285 --> Glu, Phe286 --> Ala, and His288 --> Ala in transmembrane helix M3 of the Na+,K(+)-ATPase were studied. Except for His285 --> Ala, these mutations were compatible with cell viability, permitting analysis of their effects on the overall and partial reactions of the Na+,K(+)-transport cycle. In Ile279 --> Ala and Ile283 --> Ala, the E1 form accumulated, whereas in His285 --> Lys and His285 --> Glu, E1P accumulated. Phe286 --> Ala displaced the conformational equilibria of dephosphoenzyme and phosphoenzyme in parallel in favor of E2 and E2P, respectively, and showed a unique enhancement of the E1P --> E2P transition rate. These effects suggest that M3 undergoes significant rearrangements in relation to E1-E2 and E1P-E2P conformational changes. Because the E1-E2 and E1P-E2P conformational equilibria were differentially affected by some of the mutations, the phosphorylated conformations seem to differ significantly from the dephospho forms in the M3 region. Mutation of His285 furthermore increased the Na(+)-activated ATPase activity in the absence of K+ ("Na(+)-ATPase activity"). Ile279 --> Ala, Ile283 --> Ala, and His288 --> Ala showed reduced Na+ affinity of the E1 form. The rate of Na(+)-activated phosphorylation from ATP was reduced in Ile279 --> Ala and Ile283 --> Ala, and these mutants showed evidence similar to Glu329 --> Gln of destabilization of the Na(+)-occluded state.