The effects of weight loss on skeletal muscle lactate transporter [monocarboxylate transporter (MCT)] expression in obese subjects were investigated to better understand how lactate transporter metabolism is regulated in insulin-resistant states. Ten obese subjects underwent non-macronutrient-specific energy restriction for 15 wk. Anthropometric measurements and a needle biopsy of the vastus lateralis muscle before and after the weight loss program were performed. Enzymatic activity, fiber type distribution, and skeletal muscle MCT protein expression were measured. Muscle from nonobese control subjects was used for comparison of MCT levels. The program induced a weight loss of 9.2 ± 1.6 kg. Compared with controls, muscle from obese subjects showed a strong tendency ( P = 0.06) for elevated MCT4 expression (+69%) before the weight loss program. MCT4 expression decreased (−7%) following weight loss to reach levels that were not statistically different from control levels. There were no differences in MCT1 expression between controls and obese subjects before and after weight loss. A highly predictive regression model ( R 2 = 0.93), including waist circumference, citrate synthase activity, and percentage of type 1 fibers, was found to explain the highly variable MCT1 response to weight loss in the obese group. Therefore, in obesity, MCT1 expression appears linked both to changes in oxidative parameters and to changes in visceral adipose tissue content. The strong tendency for elevated expression of muscle MCT4 could reflect the need to release greater amounts of muscle lactate in the obese state, a situation that would be normalized with weight loss as indicated by decreased MCT4 levels.
Over the last 12 years, the demographic and clinical characteristics of patients undergoing myocardial revascularization surgery have evolved rapidly. The goal of our study was to analyze the evolution of these trends and the results of these surgical interventions.We identified patients who underwent a first or second myocardial revascularization between 1993 and 2004, and we arbitrarily divided them into 2 groups: 1 cohort of patients who underwent surgery between 1993 and 1998 and 1 cohort of patients who underwent surgery between 1999 and 2004. We compared demographic and clinical characteristics between the 2 cohorts and determined which variables were significant predictors of morbidity and mortality.From 1993 to 2004, 12 202 patients underwent a first (95.5%) or second (4.5%) myocardial revascularization. Patients in the later cohort presented with a high-risk profile. They were older and had metabolic syndrome or diabetes and peripheral vascular disease. On the other hand, there were fewer active smokers in this group. Whereas the rate of postoperative infarction and renal insufficiency was higher in the second cohort, this group had a lower incidence of stroke and prolonged mechanical ventilation and shorter hospital stays. Overall, observed mortality decreased in spite of a steady increase in predicted mortality. Identified predictors of mortality were age, stroke, female sex, nonelective surgery, renal insufficiency, peripheral vascular disease, chronic obstructive pulmonary disease, ventricular dysfunction and stenosis of the left main trunk.Our study confirmed current trends that show an increase in the at-risk population with dysmetabolic syndrome in cardiac surgery, as well as constant improvements in tertiary care in anesthesia and coronary surgery.
Recent data suggest that adipose triglyceride lipase (ATGL) plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2), recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle.We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle.G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05) while G0S2 knockdown strongly reduces (-68%, p < 0.001) triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4) expression (5.4 fold, p < 0.001). Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro.Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism.
The hormone irisin has been described as increasing energy expenditure and improving glucose tolerance in mice, yet its potential role in humans remains controversial. Objective : We describe the association between circulating irisin and insulin resistance in men with wide‐ranging fitness levels and metabolic health. Methods : Fifty‐two men aged 34‐53 yrs from 4 groups were compared: sedentary non‐obese controls (BMI<25 kg/m 2 ), sedentary obese (BMI>30 kg/m 2 ), sedentary obese glucose intolerant, and non‐obese highly trained endurance active. All participants were evaluated for fitness (VO 2max ), anthropometric profile, circulating metabolic profile, insulin resistance (hyperinsulinemic‐euglycemic clamp), and baseline plasma irisin levels (EIA, Phoenix Pharamaceuticals, Inc.). Results : Baseline plasma irisin levels were significantly different between groups (ANOVA p =0.01), being lowest in trained men (1406±382 ng/mL) and highest in metabolically deteriorated glucose intolerant subjects (2040±505 ng/mL). Including all subjects, irisin levels were positively associated with percent body fat (r=0.445, p<0.01), and negatively associated with fitness (r=‐0.369, p<0.01) and insulin sensitivity (M/I, r=‐0.355, p<0.01). The strength of these associations was reduced and lost statistical significance when excluding the active individuals, except for that with insulin resistance, which was slightly increased (r=‐0.413, p<0.01). Conclusion : Plasma irisin levels are associated with decreased insulin sensitivity in men, but the association appears to be influenced by training status. Grant Funding Source : Supported by the CIHR and CRIUCPQ.
This study investigated the efficacy of ischemic preconditioning (IPC) on the recovery of maximal aerobic performance and physiological responses compared with commonly used techniques. Nine endurance athletes performed two 5-km cycling time trials (TT) interspersed by 45 minutes of recovery that included either IPC, active recovery (AR) or neuromuscular electrical stimulation (NMES) in a randomized crossover design. Performance, blood markers, arterial O2 saturation (SpO2), heart rate (HR), near-infrared spectroscopy-derived muscle oxygenation parameters and perceptual measures were recorded throughout TTs and recovery. Differences were analyzed using repeated-measures ANOVAs and Cohen's effect size (ES). The decrement in chronometric performance from TT1 to TT2 was similar between recovery modalities (IPC: -6.1 sec, AR: -7.9 sec, NMES: -5.4 sec, p = 0.84, ES 0.05). The modalities induced similar increases in blood volume before the start of TT2 (IPC: 13.3%, AR: 14.6%, NMES: 15.0%, p = 0.79, ES 0.06) and similar changes in lactate concentration and pH. There were negligible differences between conditions in bicarbonate concentration, base excess of blood and total concentration of carbon dioxide, and no difference in SpO2, HR and muscle O2 extraction during exercise (all p > 0.05). We interpreted these findings to suggest that IPC is as effective as AR and NMES to enhance muscle blood volume, metabolic by-products clearance and maximal endurance performance. IPC could therefore complement the athlete's toolbox to promote recovery.
