Skeletal muscle mitochondrial adaptations induced by long-term cigarette smoke exposure.

Because patients with chronic obstructive pulmonary disease (COPD) are often physically inactive, it is still unclear whether the lower respiratory capacity in the locomotor muscles of these patients is due to cigarette smoking per se or is secondary to physical deconditioning. Accordingly, the purpose of this study was to examine mitochondrial alterations in the quadriceps muscle of 10 mice exposed to 8 mo of cigarette smoke, a sedentary mouse model of emphysema, and 9 control mice, using immunoblotting, spectrophotometry, and high-resolution respirometry in permeabilized muscle fibers. Mice exposed to smoke displayed a twofold increase in the oxidative stress marker, 4-HNE, (P < 0.05) compared with control mice. This was accompanied by significant decrease in protein expression of UCP3 (65%), ANT (58%), and mitochondrial complexes II-V (∼60%-75%). In contrast, maximal ADP-stimulated respiration with complex I and II substrates (CON: 23.6 ± 6.6 and SMO: 19.2 ± 8.2 ρM·mg-1·s-1) or octanoylcarnitine (CON: 21.8 ± 9.0 and SMO: 16.5 ± 6.6 ρM·mg-1·s-1) measured in permeabilized muscle fibers, as well as citrate synthase activity, were not significantly different between groups. Collectively, our findings revealed that sedentary mice exposed to cigarette smoke for 8 mo, which is typically associated with pulmonary inflammation and emphysema, exhibited a preserved mitochondrial respiratory capacity for various substrates, including fatty acid, in the skeletal muscle. However, the mitochondrial adaptations induced by cigarette smoke favored the development of chronic oxidative stress, which can indirectly contribute to augment the susceptibility to muscle fatigue and exercise intolerance.NEW & NOTEWORTHY It is unclear whether the exercise intolerance and skeletal muscle mitochondrial dysfunction observed in patients with COPD is due to cigarette smoke exposure, per se, or if they are secondary consequences to inactivity. Herein, while long-term exposure to cigarette smoke induces oxidative stress and an altered skeletal muscle phenotype, cigarette smoke does not directly contribute to mitochondrial dysfunction. With this evidence, we demonstrate the critical role of physical inactivity in cigarette smoke-related skeletal muscle dysfunction.

Rectus Femoris Characteristics in Post Stroke Spasticity: Clinical Implications from Ultrasonographic Evaluation.

In stroke survivors, rectus femoris (RF) spasticity is often implicated in gait pattern alterations such as stiff knee gait (SKG). Botulinum toxin type A (BoNT-A) is considered the gold standard for focal spasticity treatment. However-even if the accuracy of injection is crucial for BoNT-A efficacy-instrumented guidance for BoNT-A injection is not routinely applied in clinical settings. In order to investigate the possible implications of an inadequate BoNT-A injection on patients' clinical outcome, we evaluated the ultrasound-derived RF characteristics (muscle depth, muscle thickness, cross-sectional area and mean echo intensity) in 47 stroke survivors. In our sample, we observed wide variability of RF depth in both hemiparetic and unaffected side of included patients (0.44 and 3.54 cm and between 0.25 and 3.16 cm, respectively). Moreover, our analysis did not show significant differences between treated and non-treated RF in stroke survivors. These results suggest that considering the inter-individual variability in RF muscle depth and thickness, injection guidance should be considered for BoNT-A treatment in order to optimize the clinical outcome of treated patients. In particular, ultrasound guidance may help the clinicians in the long-term follow-up of muscle quality.

Relative lipid oxidation associates directly with mitochondrial fusion phenotype and mitochondria-sarcoplasmic reticulum interactions in human skeletal muscle.

Disturbances in skeletal muscle lipid oxidation might induce ectopic fat deposition and lipotoxicity. Nevertheless, the cellular mechanisms that regulate skeletal muscle lipid oxidation have not been fully determined. We aimed to determine whether there was an association between relative whole body lipid oxidation and mitochondrial size or mitochondria-sarcoplasmic reticulum interactions in the skeletal muscle. Twelve healthy men were included [mean (standard deviation), 24.7 (1.5) yr old, 24.4 (2.6) kg/m2]. The respiratory quotient (RQ) was used to estimate relative lipid oxidation at rest and during exercise (50% maximal oxygen consumption, 600 kcal expended). A skeletal muscle biopsy was obtained from the vastus lateralis at rest. Transmission electron microscopy was used to determine mitochondrial size and mitochondria-sarcoplasmic reticulum interactions (≤50 nm of distance between organelles). Protein levels of fusion/fission regulators were measured in skeletal muscle by Western blot. Resting RQ and exercise RQ associated inversely with intermyofibrillar mitochondrial size (r = -0.66 and r = -0.60, respectively, P < 0.05). Resting RQ also associated inversely with the percentage of intermyofibrillar mitochondria-sarcoplasmic reticulum interactions (r = -0.62, P = 0.03). Finally, intermyofibrillar mitochondrial size associated inversely with lipid droplet density (r = -0.66, P = 0.01) but directly with mitochondria fusion-to-fission ratio (r = 0.61, P = 0.03). Our results show that whole body lipid oxidation is associated with skeletal muscle intermyofibrillar mitochondrial size, fusion phenotype, and mitochondria-sarcoplasmic-reticulum interactions in nondiabetic humans.

Super-Resolution Reconstruction for Two- and Three-Dimensional LA-ICP-MS Bioimaging.

The resolution of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) elemental bioimaging is usually constrained by the diameter of the laser spot size and is often not adequate to explore in situ subcellular distributions of elements and proteins in biological tissue sections. Super-resolution reconstruction is a method typically used for many imaging modalities and combines multiple lower resolution images to create a higher resolution image. Here, we present a super-resolution reconstruction method for LA-ICP-MS imaging by ablating consecutive layers of a biological specimen with offset orthogonal scans, resulting in a 10× improvement in resolution for quantitative measurement of dystrophin in murine muscle fibers. Layer-by-layer image reconstruction was also extended to the third dimension without the requirement of image registration across multiple thin section specimens. Quantitative super-resolution reconstruction, combined with Gaussian filtering and application of the Richardson-Lucy total variation algorithm, provided superior image clarity and fidelity in two- and three-dimensions.

Normative data of muscle fiber diameter of vastus lateralis during childhood: a field test.

INTRODUCTION: Currently, our knowledge of standard data for muscle morphology in children is largely limited to the 1969 article by Brooke and Engel (BE). In 2016, we reported normal muscle morphology from vastus lateralis biopsies in ambulant children with cerebral palsy (CP). This report compares our normal biopsy results against BE standard value criteria. METHODS: Single-blind prospective cross-sectional study design. RESULTS: Results of biopsies taken in ambulant children with CP were normal according to morphometry and light and electron microscopy; however, only 5 of 10 fulfilled the BE standard value criteria. DISCUSSION: This short report highlights the requirement for contemporary age-specific normative data from a larger number of biopsies, including typically developing children. Review of the literature suggests that biopsy material may be available from typically developing children who were control patients in research trials. This morphometric data could contribute to expanding the normative data set. Muscle Nerve 59:590-590, 2019.

Radiation-induced muscle fibrosis rat model: establishment and valuation.

BACKGROUND: Lack of animal model of radiation induced muscle fibrosis, this study aimed to establish such a model by using 90 Gy single dose irradiation to mimic clinical relevance and also to explore the potential post-irradiation regenerative mechanism. METHODS: SD rats were randomly divided into dose investigation groups and time gradient groups. Group1-6 were irradiated with a single dose of 65Gy, 70Gy, 75Gy, 80Gy, 85Gy and 90Gy respectively, and the degree of rectus femoris fibrosis in the irradiated area was detected at 4 weeks after irradiation. Group 7-9 were irradiated with a single dose of 90Gy, and the results were detected 1, 2, 4, and 8 weeks after irradiation. Then the general condition of rats was recorded. Masson staining was used to detect muscle fibrosis. The ultrastructure of muscles was observed by electron microscope, and the expression changes of satellite cell proliferation and differentiation related genes were detected by quantitative real-time-PCR. RESULTS: A single dose of 90Gy irradiation could cause muscle fibrosis in rats. As time goes on, the severity of muscle fibrosis and the expression of TGF- ß1 increased. Significant swelling of mitochondria, myofilament disarrangement and dissolution, obvious endothelial cell swelling, increased vascular permeability, decrease of blood cell, deposition of fibrosis tissue around the vessel could be found compared with the control group. At around the 4th week, the expressions of Pax7, Myf5, MyoD, MyoG, Mrf4 increased. CONCLUSION: Irradiation of 90Gy can successfully establish the rat model of radiation-induced muscle fibrosis. This model demonstrated that regenerative process was initiated by the irradiation only at an early stage, which can serve a suitable model for investigating regenerative therapy for post-radiation muscle fibrosis.

Gear Shifting of Quadriceps during Isometric Knee Extension Disclosed Using Ultrasonography.

Ultrasonography has been widely employed to estimate the morphological changes of muscle during contraction. To further investigate the motion pattern of quadriceps during isometric knee extensions, we studied the relative motion pattern between femur and quadriceps under ultrasonography. An interesting observation is that although the force of isometric knee extension can be controlled to change almost linearly, femur in the simultaneously captured ultrasound video sequences has several different piecewise moving patterns. This phenomenon is like quadriceps having several forward gear ratios like a car starting from rest towards maximal voluntary contraction (MVC) and then returning to rest. Therefore, to verify this assumption, we captured several ultrasound video sequences of isometric knee extension and collected the torque/force signal simultaneously. Then we extract the shapes of femur from these ultrasound video sequences using video processing techniques and study the motion pattern both qualitatively and quantitatively. The phenomenon can be seen easier via a comparison between the torque signal and relative spatial distance between femur and quadriceps. Furthermore, we use cluster analysis techniques to study the process and the clustering results also provided preliminary support to the conclusion that, during both ramp increasing and decreasing phases, quadriceps contraction may have several forward gear ratios relative to femur.

Antimalarial myopathy in a systemic lupus erythematosus patient with quadriparesis and seizures: a case-based review.

Weakness, seizures, and encephalopathy have a broad differential diagnosis in patients with systemic lupus erythematosus (SLE). We present a case of a 26-year-old female with a recent diagnosis of SLE who experienced a clinical deterioration with quadriparesis, seizures, and encephalopathy. Her quadriparesis was found to be secondary to biopsy-proven hydroxychloroquine-induced myopathy with concomitant inflammatory myopathy. Her seizures and encephalopathy were suspected to be multifactorial in the setting of sepsis and critical illness with possible contributions from neuropsychiatric manifestations of SLE and macrophage activation syndrome. She experienced a dramatic clinical recovery with discontinuation of hydroxychloroquine, treatment of lupus disease activity with mycophenolate mofetil and prednisone, and antibiotic treatment for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. This case-based review provides a systematic approach to quadriparesis, seizures, and encephalopathy in patients with SLE and an evidence-based discussion of antimalarial myopathy, which is of critical importance given the widespread use of antimalarial medications for rheumatologic diseases.

Adult expression of PGC-1α and -1ß in skeletal muscle is not required for endurance exercise-induced enhancement of exercise capacity.

Exercise has been shown to be the best intervention in the treatment of many diseases. Many of the benefits of exercise are mediated by adaptions induced in skeletal muscle. The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family of transcriptional coactivators has emerged as being key mediators of the exercise response and is considered to be essential for many of the adaptions seen in skeletal muscle. However, the contribution of the PGC-1s in skeletal muscle has been evaluated by the use of either whole body or congenital skeletal muscle-specific deletion. In these models, PGC-1s were never present, thereby opening the possibility to developmental compensation. Therefore, we generated an inducible muscle-specific deletion of PGC-1α and -1ß (iMyo-PGC-1DKO), in which both PGC-1α and -ß can be deleted specifically in adult skeletal muscle. These iMyo-PGC-1DKO animals were used to assess the role of both PGC-1α and -1ß in adult skeletal muscle and their contribution to the exercise training response. Untrained iMyo-PGC-1DKO animals exhibited a time-dependent decrease in exercise performance 8 wk postdeletion, similar to what was observed in the congenital muscle-specific PGC-1DKOs. However, after 4 wk of voluntary training, the iMyo-PGC-1DKOs exhibited an increase in exercise performance with a similar adaptive response compared with control animals. This increase was associated with an increase in electron transport complex (ETC) expression and activity in the absence of PGC-1α and -1ß expression. Taken together these data suggest that PGC-1α and -1ß expression are not required for training-induced exercise performance, highlighting the contribution of PGC-1-independent mechanisms.

Changes in sarcomere lengths of the human vastus lateralis muscle with knee flexion measured using in vivo microendoscopy.

Sarcomeres are the basic contractile units of muscle, and their lengths influence muscle force-generating capacity. Despite their importance, in vivo sarcomere lengths remain unknown for many human muscles. Second harmonic generation (SHG) microendoscopy is a minimally invasive technique for imaging sarcomeres in vivo and measuring their lengths. In this study, we used SHG microendoscopy to visualize sarcomeres of the human vastus lateralis, a large knee extensor muscle important for mobility, to examine how sarcomere lengths change with knee flexion and thus affect the muscle׳s force-generating capacity. We acquired in vivo sarcomere images of several muscle fibers of the resting vastus lateralis in six healthy individuals. Mean sarcomere lengths increased (p=0.031) from 2.84±0.16µm at 50° of knee flexion to 3.17±0.13µm at 110° of knee flexion. The standard deviation of sarcomere lengths among different fibers within a muscle was 0.21±0.09µm. Our results suggest that the sarcomeres of the resting vastus lateralis at 50° of knee flexion are near optimal length. At a knee flexion angle of 110° the resting sarcomeres of vastus lateralis are longer than optimal length. These results show a smaller sarcomere length change and greater conservation of force-generating capacity with knee flexion than estimated in previous studies.

Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function.

In older adults, we examined the effect of chronic muscle disuse on skeletal muscle structure at the tissue, cellular, organellar, and molecular levels and its relationship to muscle function. Volunteers with advanced-stage knee osteoarthritis (OA, n = 16) were recruited to reflect the effects of chronic lower extremity muscle disuse and compared with recreationally active controls (n = 15) without knee OA but similar in age, sex, and health status. In the OA group, quadriceps muscle and single-fiber cross-sectional area were reduced, with the largest reduction in myosin heavy chain IIA fibers. Myosin heavy chain IIAX fibers were more prevalent in the OA group, and their atrophy was sex-specific: men showed a reduction in cross-sectional area, and women showed no differences. Myofibrillar ultrastructure, myonuclear content, and mitochondrial content and morphology generally did not differ between groups, with the exception of sex-specific adaptations in subsarcolemmal (SS) mitochondria, which were driven by lower values in OA women. SS mitochondrial content was also differently related to cellular and molecular functional parameters by sex: greater SS mitochondrial content was associated with improved contractility in women but reduced function in men. Collectively, these results demonstrate sex-specific structural phenotypes at the cellular and organellar levels with chronic disuse in older adults, with novel associations between energetic and contractile systems.

Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle.

Chaperone-assisted selective autophagy (CASA) is a tension-induced degradation pathway essential for muscle maintenance. Impairment of CASA causes childhood muscle dystrophy and cardiomyopathy. However, the importance of CASA for muscle function in healthy individuals has remained elusive so far. Here we describe the impact of strength training on CASA in a group of healthy and moderately trained men. We show that strenuous resistance exercise causes an acute induction of CASA in affected muscles to degrade mechanically damaged cytoskeleton proteins. Moreover, repeated resistance exercise during 4 wk of training led to an increased expression of CASA components. In human skeletal muscle, CASA apparently acts as a central adaptation mechanism that responds to acute physical exercise and to repeated mechanical stimulation.

Ultrastructural mitochondrial alterations in equine myopathies of unknown origin.

BACKGROUND: Very few mitochondrial myopathies have been described in horses. OBJECTIVE: To examine the ultrastructure of muscle mitochondria in equine cases of myopathy of unknown origin. MATERIALS & METHODS: Biopsies of vastus lateralis of the Musculus quadriceps femoris were taken predominantly immediately post mortem and processed for transmission electron microscopy. As a result, electron micrographs of 90 horses in total were available for analysis comprising 4 control horses, 16 horses suffering from myopathy and 70 otherwise diseased horses. RESULTS: Following a thorough clinical and laboratory work-up, four out of five patients that did not fit into the usual algorithm to detect known causes of myopathy showed ultrastructural mitochondrial alterations. Small mitochondria with zones with complete disruption of cristae associated with lactic acidemia were detected in a 17-year-old pony mare, extremely long and slender mitochondria with longitudinal cristae in a 5-year-old Quarter horse stallion, a mixture of irregular extremely large mitochondria (measuring 2500 by 800 nm) next to smaller ones in an 8-year-old Hanoverian mare and round mitochondria with only few cristae in a 11-year-old pony gelding. It remains uncertain whether the subsarcolemmal mitochondrial accumulations observed in the fifth patient have any pathological significance. CONCLUSIONS: Ultrastructural alterations in mitochondria were detected in at least four horses. To conclude that these are due to mitochondrial dysfuntions, biochemical tests should be performed. PRACTICAL APPLICATIONS: The possibility of a mitochondrial myopathy should be included in the differential diagnosis of muscle weakness.

Sporadic inclusion body myositis: clinical, pathological, and genetic analysis of eight Polish patients.

INTRODUCTION: Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in patients above 50 years of age. Its progressive course finally leads to immobilisation, and no effective therapy exists. Its pathogenesis includes both degenerative and inflammatory processes, however, its direct causes remain unknown. Therefore, a possible genetic background of the disease must also be considered. MATERIAL AND METHODS: Here we report on twelve patients: eight with sporadic inclusion body myositis and four with other myopathies with rimmed vacuoles in muscle biopsy. All patients were evaluated clinically, morphologically, radiologically, and genetically. RESULTS: All patients with sIBM presented both shoulder and pelvic girdle muscle involvement. In addition, distal upper and lower limb muscle weakness was noted. Patients with other muscle disorders showed effects mainly in proximal muscles and marked calf muscle hypertrophy. In sIBM cases computed tomography of lower limb muscles revealed atrophy that was most pronounced within the quadriceps femoris and gracilis muscles in the thighs and within the medial head of the gastrocnemius muscle and the tibialis anterior muscle in the lower legs. On light microscopy mononuclear cell invasion of muscle fibres was present in six patients with sIBM. On electron microscopy myofibrillar disorganisation and mitochondrial abnormalities were noted in all sIBM patients, whereas cytoplasmic tubulofilamentous inclusions were seen in three patients and both cytoplasmic and nuclear inclusions in one of them. According to the criteria by Rose et al. (2011) six patients were classified as "clinico-pathologically defined IBM", one as "clinically defined IBM", and one as "probable IBM". Pathological deposits of TDP-43 were found in muscles in all sIBM as well as in control cases. Additionally, accumulation of other proteins thought to be associated with sIBM, like ß-amyloid, -synuclein, and tau protein, was present in the most of examined biopsies. All twelve patients were screened for the presence of causative mutations in TARDBP, VCP, HNRNPA1, and HNRNPA2B1 genes. Additionally, analysis of C9ORF72 hexanucleotide repeat expansion was performed. No causative mutations were found in any of the patients. CONCLUSIONS: Our study provides the first - to our knowledge - comprehensive clinical, pathological, and genetic workup of a group of Polish patients.

[Effects of electroacupuncture with manifestation-root acupoint combination on ultrastructure and biosynthesis in mitochondrial of quadriceps femoris in rats with insulin resistance].

OBJECTIVE: To explore the mechanism of electroacupuncture on improving insulin resistance of rat from aspects of morphology and function of mitochondrial in quadriceps femoris. METHODS: Forty-eight 8-week Wistar rats (female and male in half) were randomly divided into a normal group (16 rats, group A), a model control group (16 rats, group B), a model plus electroacupuncture (EA) group (8 rats, group C) and a model plus sham acupoint EA group (8 rats, group D). Group A was given with basic diet while high-fat diet was applied in the group B, group C and group D for 8 weeks to establish model of insulin resistance. After the model establishment, "Guanyuan" (CV 4), "Zhongwan" (CV 12), "Zusanli" (ST 36) and "Fenglong" (ST 30) were selected according to acupoint combination of manifestation-root in the group C, while four points in non-meridian area where 1 to 2 mm next to the acupoints used in group C were selected in the group D. The treatment was given 15 min per time with 1 mA of intensity and 2 Hz in frequency, 5 times per week for totally 8 weeks. The transmission electron microscope was adopted to observe mitochondria structure, and chemical colorimetry was used to test the activity of adenosine triphosphate (ATP) synthase and phosphomolybdic acid colorimetry was applied to measure the content of ATP. RESULTS: After the treatment, the body mass was (401.63 +/- 109.81) g in the group B, which was significantly higher than (305.88 +/- 62.72) g in the group A (P < 0.05); morphological structure of mitochondrion was damaged, showing swelling and deformation; the activity of ATP synthase was decreased (P < 0.05) and the content of ATP in tissue of quadriceps femoris was also obviously lowered (P < 0.05). The body mass was (294.13 +/- 53.78) g in the group C, which was significantly lower than that in the group B (P < 0.05); the damaged mitochondrion was restored and merged among each other; the activity of ATP synthase was increased (P < 0.05); the content of ATP in tissue of quadriceps femoris was obviously lifted (P < 0.05). The results in group D were not different from those in group B. CONCLUSION: The electroacupuncture with manifestation-root acupoint combination could improve the recovery of damaged structure of mitochondrion and promote the merge among each other, which could enhance oxidizing capacity, lower body mass and improve synthetic rate of ATP.

Multiple mitochondrial alterations in a case of myopathy.

Mitochondrial alterations are the most common feature of human myopathies. A biopsy of quadriceps muscle from a 50-year-old woman exhibiting myopathic symptoms was examined by transmission electron microscopy. Biopsied fibers from quadriceps muscle displayed numerous subsarcolemmal mitochondria that contained crystalloids. Numbering 1-6 per organelle, these consisted of rows of punctuate densities measuring ∼0.34 nm; the parallel rows of these dots had a periodicity of ∼0.8 nm. The crystalloids were ensconced within cristae or in the outer compartment. Some mitochondria without crystalloids had circumferential cristae, leaving a membrane-free center that was filled with a farinaceous material. Other scattered fibrocyte defects included disruption of the contractile apparatus or its sporadic replacement by a finely punctuate material in some myofibers. Intramitochondrial crystalloids, although morphologically striking, do not impair organelle physiology to a significant degree, so the muscle weakness of the patient must originate elsewhere.

Might prepatterned acetylcholine-receptor clusters on surface myotubes be a sign of neuromuscular-junction maturation failure?

INTRODUCTION: During human myogenesis and synaptogenesis, the first contact between multiaxonal nerve terminals and the primary myotube occurs at an early stage of gestation, then monoaxonal nerve terminals form and postsynaptic clusters of acetylcholine-receptor are modified and redistributed to the site of muscle-nerve contact. The aim of this study is to present the ultrastructural features of muscle and motor-junction immaturity severe enough to lead to death in the first months of life. MATERIAL AND METHODS: Ultrastructural-level analysis was carried out on the quadriceps femoris muscle of an infant born at full term with severe respiratory distress but with normal SMN1 and IGHMBP2 genes. RESULTS: Arrested muscle maturation was manifested in the presence of primary and mature myotubes, prepatterned acetylcholine-receptor clusters devoid of terminal axons, lack of synapses and multiaxonal unmyelinated intramuscular nerves. CONCLUSION: The "naked" prepatterned clusters observed on the surface of myotubes normally never observed in neonates might be a sign of a new genetic defect in innervation.

Endurance training modulates intramyocellular lipid compartmentalization and morphology in skeletal muscle of lean and obese women.

CONTEXT: The accumulation of intramyocellular lipids (IMCLs) and mitochondrial dysfunction in skeletal muscle have been associated with insulin resistance in obesity. Endurance training (ET) increases mitochondrial content/activity and IMCL content in young, active men and women. We have previously shown that ET alters the size, number, and physical juxtaposition of IMCLs and mitochondria. OBJECTIVE: The purpose of this study was to determine the effects of obesity and ET on mitochondrial function, IMCL content, and IMCL-mitochondria juxtaposition in sedentary lean and obese women. DESIGN, SETTING, SUBJECTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Obese (n = 11) and lean (n = 12), sedentary women were recruited using local advertisements and underwent 12 weeks of ET in our training facility at McMaster University. Blood and muscle biopsy samples (vastus lateralis) were collected before and after ET to measure IMCL and mitochondrial ultrastructure, mitochondrial oxidative capacity, lipid oxidation capacity, and lipid metabolism by-products. RESULTS: Obese women were insulin resistant (homeostasis model assessment of insulin resistance) compared with lean women. ET did not change body weight but increased mitochondrial oxidative and ß-oxidation capacity in both groups. ET mediated reorganization of the muscle architecture, whereby IMCL content in the subsarcolemmal region was reduced with a concomitant increase in intermyofibrillar IMCLs. ET increased the percentage of IMCLs in direct contact with mitochondria and did not alter diacylglycerol and ceramide content in either group. CONCLUSIONS: ET mediated positive changes in mitochondrial function and lipid oxidation and induced intracellular IMCL reorganization, which is reflective of greater IMCL turnover capacity in both lean and obese women.