Effects of acute exercise on lipid content and dietary lipid uptake in liver and skeletal muscle of lean and diabetic rats

\u3cp\u3eInsulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal muscle of lean and diabetic rats by use of magnetic resonance spectroscopy (MRS). After baseline measurements, rats were randomized to exercise or no-exercise groups. A subset of animals was subjected to MRS directly after 1 h of treadmill running for measurement of total intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n = 7 lean and diabetic rats). The other animals were administered\u3csup\u3e13\u3c/sup\u3eC-labeled lipids orally after treadmill visit (with or without exercise) followed by MRS measurements after 4 and 24 h to determine the\u3csup\u3e13\u3c/sup\u3eC enrichment of IHCL and IMCL (n = 8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs. lean rats (P < 0.001). Exercise did not significantly affect IHCL content but reduced IMCL by 25 ± 7 and 33 ± 4% in lean and diabetic rats (P < 0.05), respectively. Uptake of dietary lipids in liver and muscle was 2.3-fold greater in diabetic vs. lean rats (P < 0.05). Prior exercise did not significantly modulate dietary lipid uptake into muscle, but in liver of both lean and diabetic rats, lipid uptake was 44% reduced after acute exercise (P < 0.05). In conclusion, IMCL but not IHCL represents a viable substrate source during exercise in both lean and diabetic rats, and exercise differentially affects dietary lipid uptake in muscle and liver.\u3c/p\u3

Influence of prolonged endurance cycling and recovery diet on intramuscular triglyceride content in trained males

Intramuscular triglycerides (IMTG) are assumed to form an important substrate source during prolonged endurance exercise in trained males. This study investigated the effects of endurance exercise and recovery diet on IMTG content in vastus lateralis muscle. Nine male cyclists were provided with a standardized diet for 3 days, after which they performed a 3-h exercise trial at a 55% maximum workload. Before and immediately after exercise and after 24 and 48 h of recovery, magnetic resonance spectroscopy (MRS) was performed to quantitate IMTG content. Muscle biopsies were taken after 48 h of recovery to determine IMTG content by using quantitative fluorescence microscopy. The entire procedure was performed two times; in one trial, a normal diet containing 39% energy (En%) as fat was provided (NF) and in the other a typical carbohydraterich athlete's diet (LF: 24 En% fat) was provided. During exercise, IMTG content decreased by 21.4 × 3.1%. During recovery, IMTG content increased significantly in the NF trial only, reaching preexercise levels within 48 h. In accord with MRS, fluorescence microscopy showed significantly higher IMTG content in the NF compared with the LF trial, with differences restricted to the type I muscle fibers (2.1 × 0.2 vs. 1.4 × 0.2% area lipid staining, respectively). In conclusion, IMTG content in the vastus lateralis muscle declines significantly during prolonged endurance exercise in male cyclists. When a normal diet is used, IMTG contents are subsequently repleted within 48 h of postexercise recovery. In contrast, IMTG repletion is impaired substantially when a typical, carbohydrate-rich athlete's diet is used. Data obtained by quantitative fluorescence microscopy correspond well with MRS results, implying that both are valid methods to quantify IMTG content

Skeletal muscle fiber characteristics in patients with chronic heart failure:Impact of disease severity and relation with muscle oxygenation during exercise

\u3cp\u3eSkeletal muscle function in patients with heart failure and reduced ejection fraction (HFrEF) greatly determines exercise capacity. However, reports on skeletal muscle fiber dimensions, fiber capillarization, and their physiological importance are inconsistent. Twenty-five moderately impaired patients with HFrEF and 25 healthy control (HC) subjects underwent muscle biopsy sampling. Type I and type II muscle fiber characteristics were determined by immunohistochemistry. In patients with HFrEF, enzymatic oxidative capacity was assessed, and pulmonary oxygen uptake (VO2) and skeletal muscle oxygenation during maximal and moderateintensity exercise were measured using near-infrared spectroscopy. While muscle fiber cross-sectional area (CSA) was not different between patients with HFrEF and HC, the percentage of type I fibers was higher in HC (46 ± 15 vs. 37 ± 12%, respectively, P = 0.041). Fiber type distribution and CSA were not different between patients in New York Heart Association (NYHA) class II and III. Type I muscle fiber capillarization was higher in HFrE.compared with HC[capillary- to-fiber perimeter exchange (CFPE) index: 5.70 ± 0.92 vs. 5.05 ± 0.82, respectively, P = 0.027]. Patients in NYHA class III had slower VO2 and muscle deoxygenation kinetics during onset of exercise and lower muscle oxidative capacity than those in class II (P < 0.05). Also, fiber capillarization was lower but no.compared with HC. Higher CFPE index was related to faster deoxygenation (rspearman±±0.682, P±0.001), however, not to muscle oxidative capacity (r±±0.282, P± 0.216). Type I muscle fiber capillarization is higher in HFrE.compared with HC but not in patients with greater exercise impairment. Greater capillarization may positively affect VO2 kinetics by enhancing muscle oxygen diffusion. NEW & NOTEWORTHY The skeletal myopathy of chronic heart failure (HF) includes a greater percentage of fatigable type II fibers and, for less impaired patients, greater skeletal muscle fiber capillarization. Near-infrared spectroscopy measurements of skeletal muscle oxygenation indicate that greater capillarization ma.compensate for reduced blood flow in mild HF by enhancing the diffusive capacity of skeletal muscle. This thereby augments and speeds oxygen extraction during contractions, which is translated into faster pulmonary oxygen uptake kinetics.\u3c/p\u3

Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes

Context: Conflicting data exist on mitochondrial function and physical activity in type 2 diabetes mellitus (T2DM) development. Objective: The aim was to assess mitochondrial function at different stages during T2DM development in combination with physical exercise in longstanding T2DM patients. Design and Methods: We performed cross-sectional analysis of skeletal muscle from 12 prediabetic 11 longstanding T2DM male subjects and 12 male controls matched by age and body mass index. Intervention: One-year intrasubject controlled supervised exercise training intervention was done in longstanding T2DM patients. Main Outcome Measurements: Extensive ex vivo analyses of mitochondrial quality, quantity, and function were collected and combined with global gene expression analysis and in vivo ATP production capacity after 1 yr of training. Results: Mitochondrial density, complex I activity, and the expression of Krebs cycle and oxidative phosphorylation system-related genes were lower in longstanding T2DM subjects but not in prediabetic subjects compared with controls. This indicated a reduced capacity to generate ATP in longstanding T2DM patients only. Gene expression analysis in prediabetic subjects suggested a switch from carbohydrate toward lipid as an energy source. One year of exercise training raised in vivo skeletal muscle ATP production capacity by 21 +/- 2% with an increased trend in mitochondrial density and complex I activity. In addition, expression levels of beta-oxidation, Krebs cycle, and oxidative phosphorylation system-related genes were higher after exercise training. Conclusions: Mitochondrial dysfunction is apparent only in inactive longstanding T2DM patients, which suggests that mitochondrial function and insulin resistance do not depend on each other. Prolonged exercise training can, at least partly, reverse the mitochondrial impairments associated with the longstanding diabetic state. (J Clin Endocrinol Metab 97: 3261-3269, 2012

Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy

\u3cp\u3eMuscle weakness and exercise intol erance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min\u3csup\u3e-1\u3c/sup\u3e·kg body wt\u3csup\u3e-1\u3c/sup\u3e, maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt\u3csup\u3e-1\u3c/sup\u3e·day\u3csup\u3e-1\u3c/sup\u3e inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50% of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using\u3csup\u3e31\u3c/sup\u3eP-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.\u3c/p\u3