Plasma adiponectin/leptin ratio associates with subcutaneous abdominal and omental adipose tissue characteristics in women.

BACKGROUND: A better understanding of adipose tissue (AT) dysfunction, which includes morphological and functional changes such as adipocyte hypertrophy as well as impaired adipogenesis, lipid storage/mobilization, endocrine and inflammatory responses, is needed in the context of obesity. One dimension of AT dysfunction, secretory adiposopathy, often assessed as a low plasma adiponectin (A)/leptin (L) ratio, is commonly observed in obesity. The aim of this study was to examine markers of AT development and metabolism in 67 women of varying age and adiposity (age: 40-62 years; body mass index, BMI: 17-41 kg/m2) according to levels of adiponectinemia, leptinemia or the plasma A/L ratio. METHODS: Body composition, regional AT distribution and circulating adipokines were determined. Lipolysis was measured from glycerol release in subcutaneous abdominal (SCABD) and omental (OME) adipocytes under basal, isoproterenol-, forskolin (FSK)- and dibutyryl-cyclic AMP (DcAMP)-stimulated conditions. Adipogenesis (C/EBP-α/ß/δ, PPAR-γ2 and SREBP-1c) and lipid metabolism (ß2-ARs, HSL, FABP4, LPL and GLUT4) gene expression (RT-qPCR) was assessed in both fat depots. Participants in the upper versus lower tertile of adiponectin, leptin or the A/L ratio were compared. RESULTS: Basal lipolysis was similar between groups. Women with a low plasma A/L ratio were characterized by higher adiposity and larger SCABD and OME adipocytes (p<0.01) compared to those with a high ratio. In OME adipocytes, women in the low adiponectinemia tertile showed higher isoproterenol-stimulated lipolysis (0.01

Similar Recovery of Maximal Cycling Performance after Ischemic Preconditioning, Neuromuscular Electrical Stimulation or Active Recovery in Endurance Athletes.

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.

The effects of diurnal Ramadan fasting on energy expenditure and substrate oxidation in healthy men.

The study aimed to examine the effects of diurnal Ramadan fasting (RF) on substrate oxidation, energy production, blood lipids and glucose as well as body composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non-practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were additionally assessed at days 10, 20 and 30 of RF in the morning and evening. Body composition was determined by hydrodensitometry, substrate oxidation and energy production by indirect calorimetry, blood metabolic profile by biochemical analyses and energy balance by activity tracker recordings and food log analyses. A significant group×time interaction revealed that chronic RF reduced body mass and adiposity in FAST, without changing lean mass, whereas CNT subjects remained unchanged. In parallel to these findings, a significant main diurnal effect (morning v. evening) of RF on substrate oxidation (a shift towards lipid oxidation) and blood metabolic profile (a decrease in glucose and an increase in total cholesterol and TAG levels, respectively) was observed, which did not vary over the course of the Ramadan. In conclusion, although RF induces diurnal metabolic adjustments (morning v. evening), no carryover effect was observed throughout RF despite the extended daily fasting period (18·0 (sd 0·3) h) and changes in body composition.

Resistance training and cardiometabolic risk in women with metabolically healthy and unhealthy obesity.

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid-lipoprotein profile, inflammation, and glucose-insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 < p < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11-1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: -0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: -0.42 to -0.84 (small to large effects), p ˂ 0.05). Glucose-insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype.

No benefit of vitamin D supplementation on muscle function and health-related quality of life in primary cardiovascular prevention patients with statin-associated muscle symptoms: A randomized controlled trial.

BACKGROUND: Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS. OBJECTIVE: The purpose of this study was to evaluate the potential benefits of vitamin D supplementation in a randomized controlled trial. METHODS: Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS. RESULTS: Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables. CONCLUSIONS: Vitamin D supplementation does not appear to mitigate SAMS.

Impact of statin withdrawal on perceived and objective muscle function.

BACKGROUND AND AIMS: Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters. METHODS: Patients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal. RESULTS: Following withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02). CONCLUSIONS: Whether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted. TRIAL REGISTRATION: This study is registered in clinicaltrials.gov (NCT01493648).

Contribution of markers of adiposopathy and adipose cell size in predicting insulin resistance in women of varying age and adiposity.

Adipose tissue (AT) dysfunctions, such as adipocyte hypertrophy, macrophage infiltration and secretory adiposopathy (low plasma adiponectin/leptin, A/L, ratio), associate with metabolic disorders. However, no study has compared the relative contribution of these markers to cardiometabolic risk in women of varying age and adiposity. Body composition, regional AT distribution, lipid-lipoprotein profile, glucose homeostasis and plasma A and L levels were determined in 67 women (age: 40-62 years; BMI: 17-41 kg/m2). Expression of macrophage infiltration marker CD68 and adipocyte size were measured from subcutaneous abdominal (SCABD) and omental (OME) fat. AT dysfunction markers correlated with most lipid-lipoprotein levels. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR, while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Multiple regression analyses including these markers and TAG levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR. The contribution of the A/L ratio was superseded by adipose cell size in the model where the latter replaced TAGs. Finally, leptinemia was a better predictor of IR than adipocyte size and the A/L ratio in our participants sample.

Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity.

Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/ß, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPß and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001

Effects of weight loss and leptin on skeletal muscle in human subjects.

Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca(2+)-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.

Milk supplementation facilitates appetite control in obese women during weight loss: a randomised, single-blind, placebo-controlled trial.

Dairy products provide Ca and protein which may facilitate appetite control. Conversely, weight loss is known to increase the motivation to eat. This randomised controlled trial verified the influence of milk supplementation on appetite markers during weight loss. Low Ca consumer women participated in a 6-month energy-restricted programme (-2508 kJ/d or -600 kcal/d) and received either a milk supplementation (1000 mg Ca/d) or an isoenergetic placebo (n 13 and 12, respectively). Fasting appetite sensations were assessed by visual analogue scales. Anthropometric parameters and fasting plasma concentrations of glucose, insulin, leptin, ghrelin and cortisol were measured as well. Both groups showed a significant weight loss (P < 0·0001). In the milk-supplemented group, a time x treatment interaction effect showed that weight loss with milk supplementation induced a smaller increase in desire to eat and hunger (P < 0·05). Unlike the placebo group, the milk-supplemented group showed a lower than predicted decrease in fullness (-17·1 v. -8·8; -2·7 v. 3·3 mm, P < 0·05, measured v. predicted values, respectively). Even after adjustment for fat mass loss, changes in ghrelin concentration predicted those in desire to eat (r 0·56, P < 0·01), hunger (r 0·45, P < 0·05) and fullness (r -0·40, P < 0·05). However, the study did not show a between-group difference in the change in ghrelin concentration in response to the intervention. These results show that milk supplementation attenuates the orexigenic effect of body weight loss.

Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD.

BACKGROUND: Factors involved in the regulation of muscle mass in chronic obstructive pulmonary disease (COPD) are still poorly understood. Comparing the signalisation involved in muscle mass regulation between two muscles with different levels of activation within the same subjects is an interesting strategy to tease out the impact of local (muscle activity) versus systemic factors in the regulation of muscle mass. A study was undertaken to measure and compare the protein levels of p-AKT, AKT, Atrogin-1, p-p70S6K, p-4E-BP1, p-GSK3ß as well as the mRNA expression of Atrogin-1, MuRF1 and FoxO-1 in the quadriceps and the diaphragm of 12 patients with COPD and 7 controls with normal lung function. METHODS: Diaphragm biopsies were obtained during thoracic surgery and quadriceps samples were obtained from needle biopsies. Protein content and mRNA expression were measured by western blot and quantitative PCR, respectively. RESULTS: Increased mRNA expressions of Atrogin-1, MuRF1 and FoxO-1 were found in the quadriceps compared with the diaphragm only in patients with COPD. The quadriceps/diaphragm ratio for MuRF1 was higher in COPD. The protein level of p-p70S6K was decreased in the quadriceps compared with the diaphragm in patients with COPD. The quadriceps/diaphragm ratios of p-p70S6K and p-GSK3ß were lower in patients with COPD than in controls. CONCLUSIONS: These results indicate a greater susceptibility to a catabolic/anabolic imbalance favouring muscle atrophy in the quadriceps compared with the diaphragm in patients with COPD. The balance between the atrophy and hypertrophy signalling is inhomogeneous between respiratory and lower limb muscles, suggesting that local factors are likely to be involved in the regulation of muscle mass in COPD.

Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects.

Maintenance of a body weight 10% above or below that "customary" for lean or obese individuals results in respective increases or decreases in the energy expended in low levels of physical activity (nonresting energy expenditure, NREE). These changes are greater than can be accounted for by the altered body weight or composition and are due mainly to altered skeletal muscle work efficiency at low levels of power generation. We performed biochemical analysis of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle histomorphology. We found that the maintenance of a 10% reduced body weight was associated with significant declines in glycolytic (phosphofructokinase, PFK) enzyme activity and, in particular, in the ratio of glycolytic to oxidative (cytochrome c oxidase, COX) enzyme activity without significant changes in the activities of enzymes relevant to mitochondrial density, respiratory chain activity, or fuel transport; or in skeletal muscle fiber type or glycogen stores. The fractional change in the ratio of PFK/COX activity in subjects following weight loss was significantly correlated with changes in the systemic respiratory exchange ratio (RER) and measures of mechanical efficiency of skeletal muscle at low workloads (pedaling a bicycle to generate 10 or 25 W of power). Thus, predictable changes in systemic skeletal muscle biochemistry accompany the maintenance of an altered body weight and account for a significant portion of the variance in skeletal muscle work efficiency and fuel utilization at reduced body weight.

Ischemic Preconditioning Enhances Aerobic Adaptations to Sprint-Interval Training in Athletes Without Altering Systemic Hypoxic Signaling and Immune Function.

Optimizing traditional training methods to elicit greater adaptations is paramount for athletes. Ischemic preconditioning (IPC) can improve maximal exercise capacity and up-regulate signaling pathways involved in physiological training adaptations. However, data on the chronic use of IPC are scarce and its impact on high-intensity training is still unknown. We investigated the benefits of adding IPC to sprint-interval training (SIT) on performance and physiological adaptations of endurance athletes. In a randomized controlled trial, athletes included eight SIT sessions in their training routine for 4 weeks, preceded by IPC (3 × 5 min ischemia/5 min reperfusion cycles at 220 mmHg, n = 11) or a placebo (20 mmHg, n = 9). Athletes were tested pre-, mid-, and post-training on a 30 s Wingate test, 5-km time trial (TT), and maximal incremental step test. Arterial O2 saturation, heart rate, rate of perceived exertion, and quadriceps muscle oxygenation changes in total hemoglobin (Δ[THb]), deoxyhemoglobin (Δ[HHb]), and tissue saturation index (ΔTSI) were measured during exercise. Blood samples were taken pre- and post-training to determine blood markers of hypoxic response, lipid-lipoprotein profile, and immune function. Differences within and between groups were analyzed using Cohen's effect size (ES). Compared to PLA, IPC improved time to complete the TT (Mid vs. Post: -1.6%, Cohen's ES ± 90% confidence limits -0.24, -0.40;-0.07) and increased power output (Mid vs. Post: 4.0%, ES 0.20, 0.06;0.35), Δ[THb] (Mid vs. Post: 73.6%, ES 0.70, -0.15;1.54, Pre vs. Post: 68.5%, ES 0.69, -0.05;1.43), Δ[HHb] (Pre vs. Post: 12.7%, ES 0.24, -0.11;0.59) and heart rate (Pre vs. Post: 1.4%, ES 0.21, -0.13;0.55, Mid vs. Post: 1.6%, ES 0.25, -0.09;0.60). IPC also attenuated the fatigue index in the Wingate test (Mid vs. Post: -8.4%, ES -0.37, -0.79;0.05). VO2peak and maximal aerobic power remained unchanged in both groups. Changes in blood markers of the hypoxic response, vasodilation, and angiogenesis remained within the normal clinical range in both groups. We concluded that IPC combined with SIT induces greater adaptations in cycling endurance performance that may be related to muscle perfusion and metabolic changes. The absence of elevated markers of immune function suggests that chronic IPC is devoid of deleterious effects in athletes, and is thus a safe and potent ergogenic tool.

Comparing an adiposopathy approach with four popular classifications schemes to categorize the metabolic profile of postmenopausal women.

Numerous classifications are used to discern metabolically healthy obese (MHO) from metabolically abnormal obese (MAO) individuals. The goal of this study was to compare a single phenotype approach, adiposopathy (i.e., the plasma adiponectin/leptin ratio), with four commonly used classifications (International Diabetes Federation (IDF), Karelis, Lynch, Wildman), all based on obesity with other risk factors), for their ability to discern phenotypic differences between MAO and MHO postmenopausal women. Anthropometry, body composition, blood pressure, cardiorespiratory fitness (CRF), lipid-lipoprotein, hepatic, inflammatory, and adipokine profiles, as well as glucose-insulin homeostasis, were assessed in 79 obese sedentary postmenopausal women (60 ± 5 years; body mass index, BMI, 34.0 ± 3.7 kg/m2). Abdominal subcutaneous adipose tissue (SCAT) expression of selected genes involved in fatty acid metabolism and inflammation was used as markers of tissue state (n = 48). Beyond their intrinsic criteria, adiposopathy was almost as effective as the Karelis definition in discerning differences in MHO for adiposity (reduced body weight, BMI, waist circumference, and fat mass), lipid-lipoprotein (lower triacylglycerol and higher HDL-cholesterol levels, reduced atherogenic ratios) and adipokine (higher adiponectin and lower leptin levels) profiles, and glucose-insulin homeostasis (lower insulin resistance) as well as for some SCAT gene expression related to lipolysis and lipogenesis, but was the only one able to distinguish these subjects for greater CRF. The other classifications revealed fewer differences between MAO and MHO women. These data suggest that considering a marker of AT dysfunction such as adiposopathy either alone or in addition to other criteria could be potentially interesting in discerning the MHO phenotype.

Recent evolution in demographic and clinical characteristics and in-hospital morbidity in patients undergoing coronary surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals.

BACKGROUND: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance. OBJECTIVE: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL. DESIGN: Fifty-three obese Pima Indians with a mean (+/-SD) age of 27 +/- 8 y, body fat of 35 +/- 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateralis muscle, and magnetic resonance imaging of the abdomen. RESULTS: Adipocyte diameter (AD) correlated positively with body fat (P < 0.0001) and IHL (estimated from magnetic resonance imaging intensity of liver; P = 0.047). No association was found between AD and plasma adiponectin or IMCL. Plasma adiponectin negatively correlated with type II IMCL (IIA, P = 0.004; IIX, P = 0.009) or IHL (P = 0.02). In a multivariate analysis, plasma adiponectin, AD, and visceral adipose tissue (VAT) independently predicted IHL. Low insulin-mediated glucose disposal was associated with low plasma adiponectin (P = 0.02) and high IHL (P = 0.0003), SAT (P = 0.02), and VAT (P = 0.04). High IHL was the only predictor of reduced insulin-mediated suppression of hepatic glucose production (P = 0.02) and the only independent predictor of insulin-mediated glucose disposal in a multivariate analysis. CONCLUSIONS: Increased lipid content in the liver may independently link hypoadiponectinemia, hypertrophic obesity, and increased visceral adiposity with peripheral and hepatic insulin resistance.

Effect of weight loss on lactate transporter expression in skeletal muscle of obese subjects.

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 (R2 = 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.

Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

Ischemic Preconditioning Improves Time Trial Performance at Moderate Altitude.

PURPOSE: Endurance athletes often compete and train at altitude where exercise capacity is reduced. Investigating acclimation strategies is therefore critical. Ischemic preconditioning (IPC) can improve endurance performance at sea level through improved O2 delivery and utilization, which could also prove beneficial at altitude. However, data are scarce, and there is no study at altitudes commonly visited by endurance athletes. METHODS: In a randomized, crossover study, we investigated performance and physiological responses in 13 male endurance cyclists during four 5-km cycling time trials (TT), preceded by either IPC (3 × 5 min ischemia/5-min reperfusion cycles at 220 mm Hg) or SHAM (20 mm Hg) administered to both thighs, at simulated low (FIO2 0.180, ~1200 m) and moderate (FIO2 0.154, ~2400 m) altitudes. Time to completion, power output, cardiac output (Q˙), arterial O2 saturation (SpO2), quadriceps tissue saturation index (TSI) and RPE were recorded throughout the TT. Differences between IPC and SHAM were analyzed at every altitude using Cohen effect size (ES) and compared with the smallest worthwhile change. RESULTS: At low altitude, IPC possibly improved time to complete the TT (-5.2 s, -1.1%; Cohen ES ± 90% confidence limits -0.22, -0.44; 0.01), power output (2.7%; ES 0.21, 0.08; 0.51), and Q˙ (5.0%; ES 0.27, 0.00; 0.54), but did not alter SpO2, muscle TSI, and RPE. At moderate altitude, IPC likely enhanced completion time (-7.3 s; -1.5%; ES -0.38, -0.55; -0.20), and power output in the second half of the TT (4.6%; ES 0.28, -0.15; 0.72), increased SpO2 (1.0%; ES 0.38, -0.05; 0.81), and decreased TSI (-6.5%; ES -0.27, -0.73; 0.20) and RPE (-5.4%, ES -0.27, -0.48; -0.06). CONCLUSIONS: Ischemic preconditioning may provide an immediate and effective strategy to defend SpO2 and enhance high-intensity endurance performance at moderate altitude.

High-intensity interval training improves acute plasma volume responses to exercise that is age dependent.

Plasma volume (PV) is affected by several factors including age, physical training and, acutely, by exercise intensity. The purpose of this study was to investigate the effects of 6 weeks of high-intensity interval training (HIT) on PV and blood pressure (BP) changes among sedentary individuals. Thirty subjects aged between 18 and 71 years [body mass index=30.1(1.2) kg/m2 ] completed a 6-weeks HIT program. Anthropometric and fitness variables were obtained at pre- and post- HIT. PV variations during warm-up and after supramaximal cycling test (SCT) were calculated using two methods based on Hematocrit (Ht) and Hemoglobin (Hb) measures. After both the warm-up and SCT, PV decreased significantly among participants at pre- and at post-HIT (P < 0.01). However, PV decreases were significantly greater at pre-HIT compared with post-HIT during warm-up and after SCT (P < 0.01, respectively). In addition, at pre-HIT, a positive relationship was found between age and both PV variations at warm-up and after SCT (r2  = 0.55 and r2  = 0.46; P < 0.01 respectively). However, no relationship was found during the post-HIT period. After SCT and after both visits, only body weight predicted 22% of PV variations. In the current study, a significant relationship was found between systolic and diastolic BP improvements and PV variations in post-HIT (r2  = 0.54 and r2 =0.56, P < 0.05, respectively). Our results suggest that HIT may improve PV values and reduce the effects of age on the decrease in PV. These interventions led to improvements in systolic and diastolic BP values among participants.