Physical Activity and Bone Health in Schoolchildren: The Mediating Role of Fitness and Body Fat

<div><p>Background</p><p>The relationship between physical activity (PA) and bone health is well known, although the role of percent body fat (%BF) and fitness as confounders or mediators in this relationship remains uncertain.</p><p>Objective</p><p>To examine whether the association between PA and bone mineral content (BMC) is mediated by %BF and cardiorespiratory fitness (CRF).</p><p>Methods</p><p>In this cross sectional study, BMC, total %BF (by DXA), vigorous PA (VPA), CRF, age and height were measured in 132 schoolchildren (62 boys, aged 8–11 years). ANCOVA was used to test differences in BMC by %BF, CRF and VPA, controlling for different sets of confounders. Simple mediation analyses and serial multiple mediation analyses were fitted to examine whether the relationship between PA and BMC is mediated by %BF and fitness.</p><p>Results</p><p>Children with high %BF had higher total body BMC than their peers after controlling for all sets of confounders. Children with good CRF or VPA had significantly less total body BMC after controlling for age and sex but in children with good CRF this inverse relation disappeared after adjusting by %BF. %BF and CRF both act as a full mediator in the association between VPA and BMC, after inclusion of the potential confounders in the models.</p><p>Conclusion</p><p>Fitness and %BF seem to have a mediator role on the relationship between physical activity and bone mass.</p></div

Simple mediation models of the relationship of vigorous physical activity (VPA) and cardiorespiratory fitness (CRF) with bone mineral content (BMC), using percent body fat (% BF) or CRF as mediators, controlling for age.

<p>**p< 0.01 *p< 0.05</p

Partial correlation coefficients among total body bone mineral content, physical activity, total percent body fat, total lean mass and cardiorespiratory fitness in children, controlling for age.

<p>BMC bone mineral content; Total % BF Total percent body fat; TLM Total lean mass; CRF cardiorespiratory fitness; MVPA moderate to vigorous physical activity; VPA vigorous physical activity.</p><p>* p< 0.05;</p><p>**p< 0.001.</p><p>Partial correlation coefficients among total body bone mineral content, physical activity, total percent body fat, total lean mass and cardiorespiratory fitness in children, controlling for age.</p

ANCOVA models comparing means of total body bone mineral content (BMC) by total percent body fat (%BF), cardiorespiratory fitness (CRF) and vigorous physical activity (VPA) categories in children.

<p>Covariates for %BF: Model 1(age and sex); Model 2 (Model 1+ VPA); Model 3: (Model 2+CRF). Superscript letter indicates statistical significance (≤ 0.050) for post hoc hypothesis test determinates by using the Bonferroni correction for multiple comparisons:</p><p>^a High >Medium> Low;</p><p>^b High> Medium;</p><p>^c High> Low.</p><p>Covariates for CRF: Model 1(age and sex); Model 2 (Model 1+ VPA); Model 3: (Model 2+%BF) Superscript letter indicates statistical significance (≤ 0.050) for post hoc hypothesis test determinates by using the Bonferroni correction for multiple comparisons:</p><p>^a Poor> Satisfactory;</p><p>^b Poor> Good.</p><p>Covariates for VPA: Model 1(age and sex); Model 2 (Model 1+ CRF); Model 3: (Model 2+%BF). Superscript letter indicates statistical significance (≤ 0.050) for post hoc hypothesis test determinates by using the Bonferroni correction for multiple comparisons:</p><p>^a Poor> Good.</p><p>ANCOVA models comparing means of total body bone mineral content (BMC) by total percent body fat (%BF), cardiorespiratory fitness (CRF) and vigorous physical activity (VPA) categories in children.</p

Descriptive characteristics of the study sample.

<p>Values are mean ± SD.</p><p>CRF cardiorespiratory fitness; BMI body mass index; BMC bone mineral content; MVPA moderate-to-vigorous physical activity; VPA vigorous physical activity.</p><p>Descriptive characteristics of the study sample.</p

BMI mediation models of the relationship between muscular fitness and cardiometabolic risk variables, controlling for age, by sex.

<p>A: MAP; B: log fasting insulin; C: log TG/HDL-c; D: WC; E: CMRI. Data in roman type refer to boys. %Med: Percentage mediated by proposed mediator. Data in italics refer to girls. **p≤0.001; *p≤0.05.</p

Mean differences in cardiometabolic risk factors by body mass index and muscular fitness categories in girls.

<p>Data are presented as marginal estimated mean ± SE.</p><p>MAP = mean arterial blood pressure (DBP + {0.333 x (SBP—DBP)}); Log Insulin = logarithm of fasting insulin; Log TG/HDL-c = logarithm of triglyceride to high density lipoprotein cholesterol ratio. CMRI = cardiometabolic risk index.</p><p>Categories of body mass index (BMI) are Normal Weight (NW), Overweight (OW) and Obesity (OB) according to gender-and-age-specific cut-offs defined by Cole and Lobstein. Categories of muscular fitness (an index was measured by the sum of the standardized z score of dynamometry/weight and standing long jump) are Lower Q (representing 1^st quartile), Middle Q (2^nd and 3^rd quartiles), and Upper Q (4th quartile).</p><p>Model 1 controlling for age. All the pairwise mean comparisons using Bonferroni post-hoc test were statistically significant (p<0.001) (NWMiddle Q>Upper Q for muscular fitness), except for superscript letters.</p><p>Model 2 further adjustments for muscular fitness to BMI (NW</p><p>Analysis of differences in CMRI and cardiometabolic risk factors among SLJ and dynamometry/weight categories showed that the children with better MF had lower cardiometabolic risk (controlling for age); but when BMI was added as a covariate (model 2) the differences disappeared in both sexes (A–D Tables in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116506#pone.0116506.s001" target="_blank">S1 File</a>). Similar results have been found when SLJ, dynamometry and MF index were normalized by allometric parameters (E–G Tables in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116506#pone.0116506.s001" target="_blank">S1 File</a>) and also when we used residuals of body mass regression on the fitness phenotypes (data not shown).</p><p>Mean differences in cardiometabolic risk factors by body mass index and muscular fitness categories in girls.</p

Characteristics of the study sample.

<p>Characteristics of the study sample.</p

The Multifaceted Roles of PI3Kγ in Hypertension, Vascular Biology, and Inflammation

PI3Kγ is a multifaceted protein, crucially involved in cardiovascular and immune systems. Several studies described the biological and physiological functions of this enzyme in the regulation of cardiovascular system, while others stressed its role in the modulation of immunity. Although PI3Kγ has been historically investigated for its role in leukocytes, the last decade of research also dedicated efforts to explore its functions in the cardiovascular system. In this review, we report an overview recapitulating how PI3Kγ signaling participates in the regulation of vascular functions involved in blood pressure regulation. Moreover, we also summarize the main functions of PI3Kγ in immune responses that could be potentially important in the interaction with the cardiovascular system. Considering that vascular and immune mechanisms are increasingly emerging as intertwining players in hypertension, PI3Kγ could be an intriguing pathway acting on both sides. The availability of specific inhibitors introduces a perspective of further translational research and clinical approaches that could be exploited in hypertension