Comparison of energy expenditure, heart rate and breathing rate.

<p>Comparison of mean ± SEM energy expenditure (EE, Panel A), RQ (Panel B), heart rate (beats/min, Panel E), and breathing rate (breaths/min, Panel F) for each EE response group: Non-Responders (▴), Responder Droppers (□), Responder Non-Droppers (▪). The shaded area indicates the steady-state standing period. *statistically significant from baseline as assessed by repeated-measures ANOVA followed by Dunnett’s multiple comparison tests. Panels C and D indicate the relationships between the change in RQ <i>vs</i> change in EE during the first 5 min (percentage “rise” from sitting value, Panel C), as well as <i>vs</i> change in EE during the second 5 min (percentage “drop” to sitting value, Panel D) of the 10 min steady-state standing period. ΔEE (% rise) <i>vs</i> ΔRQ (1^st 5 min): r = 0.56, p<0.02; ΔEE (% drop) <i>vs</i> ΔRQ (2^nd 5 min): r = 0.77, p = 0.001. Non-Responders (▴), Responder Droppers (□), Responder Non-Droppers (▪).</p

Energy expenditure (EE) during sitting and steady-state (SS) standing.

<p>Mean ± SEM energy expenditure (EE) during sitting and steady-state (SS) standing, expressed as percentage change relative to mean sitting EE (Panel A); *statistically significant from baseline as assessed by repeated-measures ANOVA followed by Dunnett’s multiple comparison tests. In the present study the percentage change from the mean sitting value to the mean of the first 5 min of the SS-standing period is referred to as “rise” from sitting value. The percentage change from the mean of the first 5 min to the mean of the second 5 min of the SS-standing period is referred to as “drop” to sitting value. Box and whisker plot comparing rise (Panel B) and drop (Panel C) for each EE response group. NR = Non-Responders, R-DP = Responder Droppers, R-ND = Responder Non-Droppers.</p

Experimental design and time-line.

<p>Schema of experimental design. Posture-adapted ventilated hood indirect calorimetry set-up for sitting and standing measurements (Panel A). The shaded area shows that the area of the subject covered by the veil of the ventilated hood. 1 = air inlet; 2 = air outlet to Deltatrac. Diagrammatic representation of experimental time-line (Panel B). The shaded areas represent the time periods during which minute-by-minute EE and RQ measurements were recorded. A minimum of 15 min of stable measurements were recorded during each sitting period. During postural transition (from sitting-standing, and standing-sitting) the ventilated hood was removed and no measurements recorded. The 10 min steady-state standing period was further divided into two 5 min blocks for data analysis, referred to as “1^st 5 min” (minutes 3 to 7, inclusive) and “2^nd 5 min” (minutes 8 to 12, inclusive) of the SS-standing period, respectively.</p

ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA/AMPK signaling in advanced atherosclerosis

<p>Impaired autophagy function and enhanced ARG2 (arginase 2)-MTOR (mechanistic target of rapamycin) crosstalk are implicated in vascular aging and atherosclerosis. We are interested in the role of ARG2 and the potential underlying mechanism(s) in modulation of endothelial autophagy. Using human nonsenescent “young” and replicative senescent endothelial cells as well as <i>Apolipoprotein E</i>-deficient (<i>apoe</i>^−/−<i>Arg2</i>^+/+) and <i>Arg2</i>-deficient <i>apoe</i>^−/− (<i>apoe</i>^−/−<i>arg2</i>^−/−) mice fed a high-fat diet for 10 wk as the atherosclerotic animal model, we show here that overexpression of ARG2 in the young cells suppresses endothelial autophagy with concomitant enhanced expression of RICTOR, the essential component of the MTORC2 complex, leading to activation of the AKT-MTORC1-RPS6KB1/S6K1 (ribosomal protein S6 kinase, 70kDa, polypeptide 1) cascade and inhibition of PRKAA/AMPK (protein kinase, AMP-activated, α catalytic subunit). Expression of an inactive ARG2 mutant (H160F) had the same effect. Moreover, silencing RPS6KB1 or expression of a constitutively active PRKAA prevented autophagy suppression by ARG2 or H160F. In senescent cells, enhanced ARG2-RICTOR-AKT-MTORC1-RPS6KB1 and decreased PRKAA signaling and autophagy were observed, which was reversed by silencing <i>ARG2</i> but not by arginase inhibitors. In line with the above observations, genetic ablation of <i>Arg2</i> in <i>apoe</i>^−/− mice reduced RPS6KB1, enhanced PRKAA signaling and endothelial autophagy in aortas, which was associated with reduced atherosclerosis lesion formation. Taken together, the results demonstrate that ARG2 impairs endothelial autophagy independently of the L-arginine ureahydrolase activity through activation of RPS6KB1 and inhibition of PRKAA, which is implicated in atherogenesis.</p

Mean (± SEM) intra- and inter-frequency coefficient of variation (CV %) of energy expenditure in 4 individual subjects across 3 days.

<p>Panel A: raw EE; Panel B: delta EE from seated resting EE (REE); Panel C: delta EE from standing with no vibration (NV). Black bars represent mean intra-frequency (inter-day) CV ± SEM, white bars represent mean inter-frequency (intra-day) CV.</p

Energy Expenditure and Substrate Oxidation in Response to Side-Alternating Whole Body Vibration across Three Commonly-Used Vibration Frequencies - Fig 1

<p>Panel A: Schema showing experimental protocol for intermittent side-alternating whole body vibration (WBV) across varying frequencies. Black bars represent periods of WBV, with each frequency (30, 40 or 50 Hz) assessed over 5 cycles of 30 s vibration and 30 s rest (on the platform), and separated by 5 min rest on a comfortable chair. EE at each vibration frequency was calculated as the integrated mean across the entire 5 min intermittent WBV period (i.e., including measurements obtained during both the 30 s vibration and 30 s rest intervals). Black bars indicate vibration periods. REE: resting energy expenditure while sitting in a comfortable seat (sit); NV: participant standing on platform with no vibration. Panel B: Photo of the position adopted by subjects on the vibrating platform.</p

Effects of three frequencies of intermittent side-alternating whole-body vibration (WBV) on energy expenditure (EE) in 4 individual subjects across 3 days (D1-D3).

<p>White bars: standing, no vibration (NV); black bars: WBV.</p

Effects of three frequencies of intermittent side-alternating whole-body vibration (WBV) on energy expenditure (EE) and respiratory quotient (RQ).

<p>Left-hand panels (A, C, E) show EE and RQ measured in 8 healthy, young adults across a range of vibration frequencies (30–50 Hz) compared to standing with no vibration. Right-hand panels (B, D, F) show EE and RQ measured across three consecutive vibration periods in 6 healthy, young men at a fixed frequency of 40 Hz. White bars: standing, no vibration (NV); black bars: WBV. Panels A & B: WBV frequencies not sharing letter (<i>a</i>,<i>b</i>) are different from one another, as assessed by repeated measures ANOVA followed by Tukey HSD All-Pairwise Comparisons Test.</p

Effects of three frequencies of intermittent side-alternating whole-body vibration (WBV) on energy expenditure (EE) in 8 individual subjects.

<p>White bars: standing, no vibration (NV); black bars: WBV.</p

Resveratrol reduces superoxide generation and enhances NO production in senescent endothelial cells.

<p>Young and senescent HUVEC cells were treated with solvent as control (C), resveratrol (Resv, 10 µmol/L) or rapamycin (Rapa, 20 ng/ml) for one hour and then subjected to (<b>A</b>) MitoSox, (<b>B</b>) DHE, and (<b>C</b>) DAF-2DA staining. Quantification of the signals from six independent experiments is shown in the corresponding right panels. *p<0.05, **p<0.01 and ***p<0.001 between indicated groups. Scale bar = 0.2 mm.</p