Effects of antiretroviral therapy on proprotein convertase subtilisin/kexin 9: focus on lipids, inflammation and immunovirological parameters.

OBJECTIVES: Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol metabolism, have been reported to have an increasing trend in people living with HIV (PLWH) compared with controls. We assessed the impact of different antiretroviral (ARV) regimens on plasma PCSK9 levels as well as plasma lipids, systemic inflammation and immunovirological parameters. METHODS: Eighty HIV-positive ARV therapy (ART)-naïve PLWH and 40 uninfected controls were retrospectively enrolled. At baseline and 3, 6 and 12 months after ART initiation, plasma PCSK9 levels, lipids, high-sensitivity C-reactive protein (hs-CRP), HIV-1 RNA levels and CD4 T-cell count were measured. RESULTS: Baseline PCSK9 levels were significantly more elevated in PLWH and were associated with HIV-1 RNA levels (P < 0.001), CD4 T-cell counts (P < 0.001), triglycerides (P < 0.001) and high-density lipoprotein (HDL) cholesterol (P < 0.001), but not with total cholesterol, low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels. The prescription of ART was paralleled by significant decreases in plasma PCSK9 and hs-CRP levels, and increases in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and lipoprotein(a), independent of regimen. CONCLUSIONS: PCSK9 levels, along with systemic inflammation, were progressively reduced following the initiation of an effective ART. However, at the end of the study PCSK9 levels remained higher than in controls and did not correlate with any of the lipid variables.

Effects of low- and high-intensity exercise training on body composition and substrate metabolism in obese adolescents.

The objective was to investigate the effects of a 3- week weight-management program including moderate energy restriction and exercise training at 2 intensities [low intensity (LI): 40% and high intensity (HI): 70% maximal oxygen uptake (V'O(2)max)] on body composition, energy expenditure, and fat oxidation rate in severely obese adolescents. Twenty obese adolescents, aged 15-17 yr (body mass index: 37.5 kg/m(2); 38.2% fat mass) participated in this study. Before starting (week 0, W0) and at the end of the weight-management period (week 3,W3), body composition was assessed by a multifrequency tetrapolar impedancemeter; basal metabolic rate (BMR), energy expenditure, and substrate oxidation rate during exercise and post-exercise recovery by indirect calorimetry. At W3, body mass and fat mass decreased significantly (p<0.005) in all groups, and the decreases were significantly greater in the LI than in the HI group (-8.1±1.6 vs -5.9±1.6 kg and -4.2±1.9 vs -2.3±1.7 kg, p<0.05, respectively). Predicted V'O(2)max, expressed in relative values, changed significantly only in the HI group by +0.010±0.006 l/(kg fat-free mass × min) (p=0.010). By contrast, no significant changes were observed at W3 in BMR, energy expenditure, and substrate oxidation rate during exercise and post-exercise recovery. In conclusion, LI (40% of V'O(2)max) physical activity favors fat oxidation and it seems advisable to encourage obese adolescents to perform LI physical activity which is more feasible and acceptable than intense exercise.

Metabolic responses to submaximal treadmill walking and cycle ergometer pedalling in obese adolescents.

Physical activity is essential in obesity management because of the impact of exercise-related energy expenditure (EE) and fat oxidation (Fox) rate on a daily balance, but the specific physiological effects of different exercise modalities are scarcely known in obese individuals. The objective of the study was to compare the metabolic responses to treadmill (TM) and cycle ergometer (CE) exercise in obese adolescents. Gas exchange, heart rate (HR), blood lactate (LA) concentration, EE and Fox were determined at different intensity levels (up to about 85% of maximal oxygen uptake) during TM and CE in 14 pubertal (Tanner stage: >3) obese (BMI SDS: 2.15-3.86) male adolescents (age: 13-18 years). At comparable HR, oxygen uptake, EE and Fox were higher, and LA lower, during TM than CE (P<0.05-0.001), suggesting that cycling imposes a metabolic involvement at the level of the single active muscles greater than walking. Therefore, due to different physiological responses to TM and CE, walking was more convenient than cycling in obese adolescents, permitting to attain the same EE at lower HR, with lower blood LA concentration and with greater Fox. These conclusions seem clinically relevant when using exercise as a part of multidisciplinary treatment for juvenile obesity and amelioration of related metabolic disturbances.

The energy cost of cycling and aerobic performance of obese adolescent girls.

In order to assess the energy cost of cycling and aerobic capacity in juvenile obesity, responses to cycle ergometer exercise were studied in 10 pubertal obese (OB) [body mass index (BMI) SD score (SDS): 3.40+/-0.58 SD] adolescent girls (age: 16.0+/-1.2 yr) and in 10 normal-weight (NW, BMI SDS: -0.30+/-0.54) girls of the same age (15.1+/-1.9). To this aim, gas exchange, heart rate (HR), and energy expenditure (EE) were studied during graded cycle ergometer test at 40, 60, 80, 100, and 120 W. The energy cost of cycling was higher in OB, being oxygen uptake (VO2) higher (about 20%) in OB than in NW girls at all workloads (p<0.01-0.001). Estimated maximal VO2 and VO2 at anaerobic threshold were significantly (p<0.05) higher in OB girls [although lower per unit body mass (p<0.01) and similar for unit fat-free mass], and explained the higher oxygen pulse and lower HR for any EE observed during submaximal exercise in OB. While net mechanical efficiency (ME) was significantly lower in OB (p<0.01), delta ME was similar in both groups, indicating no substantial derangement of muscle intrinsic efficiency. It is concluded that, despite a higher cost of cycling, OB girls can rely on a larger aerobic capacity which makes them able to sustain this kind of exercise within a wide range of work loads, with relevant implications when planning protocols of physical activity in the context of interventions for the reduction of juvenile obesity.

Physical activity ratios for various commonly performed sedentary and physical activities in obese adolescents.

The physical activity ratio (PAR) values are commonly used to convert subjects' physical activity recalls into estimates of daily energy expenditure (DEE). A PAR is defined as the ratio between energy expenditure corresponding to a sedentary or a physical activity (kJ/min) and basal metabolic rate [(BMR) kJ/min]. The objective of the present study was to determine the PAR for different sedentary and physical activities in obese adolescents. Thirty-three obese adolescents [mean body mass index: 35.1 kg/m2; 40.3 % fat mass] aged 11 to 17 yr participated in this study. BMR was assessed by indirect calorimetry after an overnight fast by means of an open-circuit, indirect computerised calorimetry with a rigid, transparent, ventilated canopy. Energy expenditures corresponding to various sedentary and physical activities in free-living conditions were determined using a portable metabolic unit, and body composition by bioelectrical impedance analysis (BIA). The PAR of each activity was obtained by dividing the assessed energy expenditure by BMR. In this study, the PAR of various sedentary and physical activities did not vary significantly with sex, age, and body mass. Thus, the data for boys and girls were combined and the PAR for 27 sedentary and physical activities were determined. The PAR values can be applied to determine the mean DEE (kJ) using the specific equation considering BMR (kJ/min), PAR, and duration (min) of each activity performed by the subject during the 24 h. This information will be useful to health-care professionals because estimation of DEE in obese adolescents is necessary in order to prescribe an adequate dietary therapy to induce a desired level of energy deficit.