The effect of a weighted pre-event movement exercise on knee extensor reaction time

BACKGROUND: Pre-Event movement with weighted objects (PEmWO) to gain a performance advantage is commonly done. The effect that PEmWO has on enhancing performance is unclear. This study\u27s purpose was to investigate the effect PEmWO has on knee extension reaction time (RT) and electromyography (EMG) onset time. METHODS: RT and EMG onset time was measured before and after doing a pre-event movement leg exercise using three weights: 8.90, 17.79, and 26.69 Newtons attached to the participant\u27s shank while the participant extended their leg five times after a random visual \u27GO\u27 to move signal. Based on the participant\u27s effort and comfort level, one of these weights was chosen as their baseline. PEmWO exercises were then randomly performed with weighted cuffs of 1/2, equal or 2xs the baseline weight. Each PEmWO consisted of 10 leg extensions with each weight. RT s and EMG onset times were calculated and compared with baseline values. RESULTS: Significant mean differences in RT or EMG onset times were not found among any of the weighted trials. However, in 13% of the participants a substantial increase was observed. CONCLUSIONS: Translating our results to actual athletic performance suggests that weighted PEmWO in most people has no advantage in decreasing the time it takes to initiate a movement. It is suggested when PEmWO exercise is used before an athletic event the lighter weighted object should be used decreasing the possibility of injury. It is also recommended that an assessment be conducted before the event is performed to assure that PEmWO is not having a detrimental effect on the athlete\u27s performance

EA.hy926 Cells and HUVECs Share Similar Senescence Phenotypes but Respond Differently to the Senolytic Drug ABT-263

Doxorubicin (DOX) induces endothelial cell (EC) senescence, which contributes to endothelial dysfunction and cardiovascular complications. Senolytic drugs selectively eliminate senescent cells to ameliorate senescence-mediated pathologies. Previous studies have demonstrated differences between immortalized and primary EC models in some characteristics. However, the response of DOX-induced senescent ECs to senolytics has not been determined across these two models. In the present work, we first established a comparative characterization of DOX-induced senescence phenotypes in immortalized EA.hy926 endothelial-derived cells and primary human umbilical vein EC (HUVECs). Thereafter, we evaluated the senolytic activity of four senolytics across both ECs. Following the DOX treatment, both EA.hy926 and HUVECs shared similar senescence phenotypes characterized by upregulated senescence markers, increased SA-β-gal activity, cell cycle arrest, and elevated expression of the senescence-associated secretory phenotype (SASP). The potentially senolytic drugs dasatinib, quercetin, and fisetin demonstrated a lack of selectivity against DOX-induced senescent EA.hy926 cells and HUVECs. However, ABT-263 (Navitoclax) selectively induced the apoptosis of DOX-induced senescent HUVECs but not EA.hy926 cells. Mechanistically, DOX-treated EA.hy926 cells and HUVECs demonstrated differential expression levels of the BCL-2 family proteins. In conclusion, both EA.hy926 cells and HUVECs demonstrate similar DOX-induced senescence phenotypes but they respond differently to ABT-263, presumably due to the different expression levels of BCL-2 family proteins

Vitamin E and age alter liver mitochondrial morphometry

Oxidative damage to mitochondrial membranes caused by free radical production during respiration plays a major role in tissue dysfunction. It has been hypothesized that aging is associated with mitochondrial enlargement and elongation. These changes may be enhanced by deficiencies in vitamin E and selenium. Vitamin E supplementation minimizes the age-related mitochondrial enlargement and elongation in the mouse liver. This study investigated the effects of vitamin E supplementation (500 IU/kg) on old (760 days) and older (827 days) C57BL/6 mice liver mitochondrial (Mt) morphometry. Fixed mitochondria from homogenized liver samples taken from control and vitamin E-supplemented mice were examined by transmission electron microscopy and measured by image analysis. Morphometric measurements included Mt area, short and long axis, and size distributions. Old vitamin E-supplemented mice had significantly smaller (p \u3c 0.0001) liver mitochondria than age-matched controls. While age had no significant effect on Mt area and short axis in the vitamin E-supplemented mice, it had a significant effect (p \u3c 0.002) on the long axis. Analysis of the long axis to short axis ratio indicated that age had a significant effect of mitochondrial elongation in the vitamin E fed mice. Vitamin E supplementation results in smaller mouse liver mitochondria as compared to age-matched cohorts and aging results in elongation but does not alter the size of liver mitochondria in mice supplemented with vitamin E. These results suggest that vitamin E provides a protective effect against age-related mitochondrial enlargement

Adipocyte specific HO-1 gene therapy is effective in antioxidant treatment of insulin resistance and vascular function in an obese mice model

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity

Adipocyte Specific HO-1 Gene Therapy is Effective in Antioxidant Treatment of Insulin Resistance and Vascular Function in an Obese Mice Model

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity

Adipocyte Specific HO-1 Gene Therapy Is Effective in Antioxidant Treatment of Insulin Resistance and Vascular Function in an Obese Mice Model

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity

High Fat Diet-Induced Obesity and Insulin Resistance in Cyp4a14-/- Mice is Mediated by 20-HETE

20-hydroxyeicosatetraenoic acid (20-HETE) has been shown to positively correlate with body mass index, hyperglycemia and plasma insulin levels. This study seeks to identify a causal relationship between 20-HETE and obesity-driven insulin resistance. Cyp4a14(-/-) male mice, a model of 20-HETE overproduction, were fed a regular or high-fat diet (HFD) for 15 weeks. 20-SOLA, a 20-HETE antagonist, was administered from week 0 or week 7 of HFD. HFD-fed mice gained significant weight (16.7+/-3.2 vs. 3.8+/-0.35 g, p\u3c0.05) and developed hyperglycemia (157+/-3 vs 121+/-7 mg/dl, p\u3c0.05) and hyperinsulinemia (2.3+/-0.4 vs 0.5+/-0.1 ng/ml, p\u3c0.05) compared to regular diet-fed mice. 20-SOLA attenuated HFD-induced weight gain (9.4+/-1 vs 16.7+/-3 g, p\u3c0.05), and normalized the hyperglycemia (157+/-7 vs 102+/-5 mg/dl, p\u3c0.05) and hyperinsulinemia (1.1+/-0.1 vs 2.3+/-0.4 ng/ml, p\u3c0.05). The impaired glucose homeostasis and insulin resistance in HFD-fed mice evidenced by reduced insulin and glucose tolerance were also ameliorated by 20-SOLA. Circulatory and adipose tissue 20-HETE levels significantly increased in HFD-fed mice correlating with impaired insulin signaling, including reduction in insulin receptor tyrosine (Y972) phosphorylation and increased serine (S307) phosphorylation of the insulin receptor substrate-1 (IRS-1). 20-SOLA treatments prevented changes in insulin signaling. These findings indicate that 20-HETE contributes to HFD-induced obesity, insulin resistance and impaired insulin signaling