Bilinguals from Larynx to Lips: Exploring Bilingual Articulatory Strategies with Anatomic MRI Data.

The goal of this article is to illustrate the use of MRI for exploring bi- and multi-lingual articulatory strategies. One male and one female speaker recorded sets of static midsagittal MRIs of the whole vocal tract, producing vowels as well as consonants in various vowel contexts in either the male's two or the female's three languages. Both speakers were native speakers of English (American and Australian English, respectively), and both were fluent L2 speakers of French. In addition, the female speaker was a heritage speaker of Croatian. Articulatory contours extracted from the MRIs were subsequently used at three progressively more compact and abstract levels of analysis. (1) Direct comparison of overlaid contours was used to assess whether phones analogous across L1 and L2 are similar or dissimilar, both overall and in specific vocal tract regions. (2) Consonant contour variability along the vocal tract due to vowel context was determined using dispersion ellipses and used to explore the variable resistance to coarticulation for non-analogous rhotics and analogous laterals in Australian, French, and Croatian. (3) Articulatory modeling was used to focus on specific articulatory gestures (tongue position and shape, lip protrusion, laryngeal height, etc.) and then to explore the articulatory strategies in the speakers' interlanguages for production of the French front rounded vowel series. This revealed that the Australian and American speakers used different strategies to produce the non-analogous French vowel series. We conclude that MRI-based articulatory data constitute a very rich and underused source of information that amply deserves applications to the study of L2 articulation and bilingual and multi-lingual speech.

Rehabilitation of speech disorders following glossectomy, based on ultrasound visual illustration and feedback.

Intraoral surgery for tongue cancer usually induces speech disorders that have a negative impact on communication and quality of life. Studies have documented the benefit of tongue ultrasound imaging as a visual articulatory feedback for speech rehabilitation. This study aims to assess specifically the complementary contribution of visual feedback to visual illustration (i.e. the display of ultrasound video of target language movements) for the speech rehabilitation of glossectomised patients. Two therapy conditions were used alternately for ten glossectomised French patients randomly divided into two cohorts. The IF cohort benefitted from 10 sessions using illustration alone (IL condition) followed by 10 sessions using illustration supplemented by visual feedback (IL+F condition). The FI cohort followed the opposite protocol, i.e. the first 10 sessions with the IL+F condition, followed by 10 sessions with the IL condition. Phonetic accuracy (Percent Consonants Correct) was monitored at baseline (T0, before the first series) and after each series (T1 and T2) using clinical speech-language assessments. None of the contrasts computed between the two conditions, using logistic regression with random effects models, were found to be statistically significant for the group analysis of assessment scores. Results were significant for a few individuals, with balanced advantages in both conditions. In conclusion, the use of articulatory visual feedback does not seem to bring a decisive advantage over the use of visual illustration, though speech therapists and patients reported that ultrasound feedback was useful at the beginning. This result should be confirmed by similar studies involving other types of speech disorders.

A muscle-specific UBE2O/AMPKα2 axis promotes insulin resistance and metabolic syndrome in obesity.

Ubiquitin-conjugating enzyme E2O (UBE2O) is expressed preferentially in metabolic tissues, but its role in regulating energy homeostasis has yet to be defined. Here we find that UBE2O is markedly upregulated in obese subjects with type 2 diabetes and show that whole-body disruption of Ube2o in mouse models in vivo results in improved metabolic profiles and resistance to high-fat diet-induced (HFD-induced) obesity and metabolic syndrome. With no difference in nutrient intake, Ube2o-/- mice were leaner and expended more energy than WT mice. In addition, hyperinsulinemic-euglycemic clamp studies revealed that Ube2o-/- mice were profoundly insulin sensitive. Through phenotype analysis of HFD mice with muscle-, fat-, or liver-specific knockout of Ube2o, we further identified UBE2O as an essential regulator of glucose and lipid metabolism programs in skeletal muscle, but not in adipose or liver tissue. Mechanistically, UBE2O acted as a ubiquitin ligase and targeted AMPKα2 for ubiquitin-dependent degradation in skeletal muscle; further, muscle-specific heterozygous knockout of Prkaa2 ablated UBE2O-controlled metabolic processes. These results identify the UBE2O/AMPKα2 axis as both a potent regulator of metabolic homeostasis in skeletal muscle and a therapeutic target in the treatment of diabetes and metabolic disorders.

Characterization of inter-speaker articulatory variability: A two-level multi-speaker modelling approach based on MRI data.

Speech communication relies on articulatory and acoustic codes shared between speakers and listeners despite inter-individual differences in morphology and idiosyncratic articulatory strategies. This study addresses the long-standing problem of characterizing and modelling speaker-independent articulatory strategies and inter-speaker articulatory variability. It explores a multi-speaker modelling approach based on two levels: statistically-based linear articulatory models, which capture the speaker-specific articulatory variability on the one hand, are in turn controlled by a speaker model, which captures the inter-speaker variability on the other hand. A low dimensionality speaker model is obtained by taking advantage of the inter-speaker correlations between morphology and strategy. To validate this approach, contours of the vocal tract articulators were manually segmented on midsagittal MRI data recorded from 11 French speakers uttering 62 vowels and consonants. Using these contours, multi-speaker models with 14 articulatory components and two morphology and strategy components led to overall variance explanations of 66%-69% and root-mean-square errors of 0.36-0.38 cm obtained in leave-one-out procedure over the speakers. Results suggest that inter-speaker variability is more related to the morphology than to the idiosyncratic strategies and illustrate the adaptation of the articulatory components to the morphology.

Which way to the dawn of speech?: Reanalyzing half a century of debates and data in light of speech science.

Recent articles on primate articulatory abilities are revolutionary regarding speech emergence, a crucial aspect of language evolution, by revealing a human-like system of proto-vowels in nonhuman primates and implicitly throughout our hominid ancestry. This article presents both a schematic history and the state of the art in primate vocalization research and its importance for speech emergence. Recent speech research advances allow more incisive comparison of phylogeny and ontogeny and also an illuminating reinterpretation of vintage primate vocalization data. This review produces three major findings. First, even among primates, laryngeal descent is not uniquely human. Second, laryngeal descent is not required to produce contrasting formant patterns in vocalizations. Third, living nonhuman primates produce vocalizations with contrasting formant patterns. Thus, evidence now overwhelmingly refutes the long-standing laryngeal descent theory, which pushes back "the dawn of speech" beyond ~200 ka ago to over ~20 Ma ago, a difference of two orders of magnitude.

Speech recovery and language plasticity can be facilitated by Sensori-Motor Fusion training in chronic non-fluent aphasia. A case report study.

The rehabilitation of speech disorders benefits from providing visual information which may improve speech motor plans in patients. We tested the proof of concept of a rehabilitation method (Sensori-Motor Fusion, SMF; Ultraspeech player) in one post-stroke patient presenting chronic non-fluent aphasia. SMF allows visualisation by the patient of target tongue and lips movements using high-speed ultrasound and video imaging. This can improve the patient's awareness of his/her own lingual and labial movements, which can, in turn, improve the representation of articulatory movements and increase the ability to coordinate and combine articulatory gestures. The auditory and oro-sensory feedback received by the patient as a result of his/her own pronunciation can be integrated with the target articulatory movements they watch. Thus, this method is founded on sensorimotor integration during speech. The SMF effect on this patient was assessed through qualitative comparison of language scores and quantitative analysis of acoustic parameters measured in a speech production task, before and after rehabilitation. We also investigated cerebral patterns of language reorganisation for rhyme detection and syllable repetition, to evaluate the influence of SMF on phonological-phonetic processes. Our results showed that SMF had a beneficial effect on this patient who qualitatively improved in naming, reading, word repetition and rhyme judgment tasks. Quantitative measurements of acoustic parameters indicate that the patient's production of vowels and syllables also improved. Compared with pre-SMF, the fMRI data in the post-SMF session revealed the activation of cerebral regions related to articulatory, auditory and somatosensory processes, which were expected to be recruited by SMF. We discuss neurocognitive and linguistic mechanisms which may explain speech improvement after SMF, as well as the advantages of using this speech rehabilitation method.

Long-term PGC1ß overexpression leads to apoptosis, autophagy and muscle wasting.

Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1α) and its splice variant PGC1α4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1ß, on muscle size is unclear. In transgenic mice selectively over-expressing PGC1ß in the skeletal muscle, we have found that PGC1ß progressively decreases skeletal muscle mass predominantly associated with loss of type 2b fast-twitch myofibers. Paradoxically, PGC1ß represses the ubiquitin-proteolysis degradation pathway genes resulting in ubiquitinated protein accumulation in muscle. However, PGC1ß overexpression triggers up-regulation of apoptosis and autophagy genes, resulting in robust activation of these cell degenerative processes, and a concomitant increase in muscle protein oxidation. Concurrently, PGC1ß up-regulates apoptosis and/or autophagy transcriptional factors such as E2f1, Atf3, Stat1, and Stat3, which may be facilitating myopathy. Therefore, PGC1ß activation negatively affects muscle mass over time, particularly fast-twitch muscles, which should be taken into consideration along with its known aerobic effects in the skeletal muscle.

A Comparative Study of the Precision of Carstens and Northern Digital Instruments Electromagnetic Articulographs.

Purpose: This study compares the precision of the electromagnetic articulographs used in speech research: Northern Digital Instruments' Wave and Carstens' AG200, AG500, and AG501 systems. Method: The fluctuation of distances between 3 pairs of sensors attached to a manually rotated device that can position them inside the measurement volumes was determined. For each device, 2 precision estimates made on the basis of the 95% quantile range of these distances (QR95) were defined: The local QR95 was computed for bins around specific rotation angles, and the global QR95 was computed for all angles pooled. Results: For all devices, although the local precision lies around 0.1 cm, the global precision is much more worrisome, ranging from 0.03 cm to 2.18 cm, and displays large variations as a function of the position of the sensors in the measurement volume. No influence of the rotational speed was found. The AG501 produced-by far-the lowest errors, in particular concerning the global precision. Conclusions: The local precision can be considered suitable for speech articulatory measurements, but the variations of the global precision need to be taken into account by the knowledge of the spatial distribution of errors. A guideline for good practice in EMA recording is proposed for each system.

Muscle Arnt/Hif1ß Is Dispensable in Myofiber Type Determination, Vascularization and Insulin Sensitivity.

Aryl Hydrocarbon Receptor Nuclear Translocator/ hypoxia-inducible factor 1 beta (ARNT/ HIF1ß), a member of bHLH-PAS family of transcriptional factors, plays a critical role in metabolic homeostasis, insulin resistance and glucose intolerance. The contributions of ARNT in pancreas, liver and adipose tissue to energy balance through gene regulation have been described. Surprisingly, the impact of ARNT signaling in the skeletal muscles, one of the major organs involved in glucose disposal, has not been investigated, especially in type II diabetes. Here we report that ARNT is expressed in the skeletal muscles, particularly in the energy-efficient oxidative slow-twitch myofibers, which are characterized by increased oxidative capacity, mitochondrial content, vascular supply and insulin sensitivity. However, muscle-specific deletion of ARNT did not change myofiber type distribution, oxidative capacity, mitochondrial content, capillarity, or the expression of genes associated with these features. Consequently, the lack of ARNT in the skeletal muscle did not affect weight gain, lean/fat mass, insulin sensitivity and glucose tolerance in lean mice, nor did it impact insulin resistance and glucose intolerance in high fat diet-induced obesity. Therefore, skeletal muscle ARNT is dispensable for controlling muscle fiber type and metabolic regulation, as well as diet-induced weight control, insulin sensitivity and glucose tolerance.

Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle.

Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges. We show that PLIN5 protein is elevated in endurance-trained (ET) subjects and correlates with muscle oxidative capacity and whole-body insulin sensitivity. When overexpressed in human skeletal muscle cells to recapitulate the ET phenotype, PLIN5 diminishes lipolysis and FA oxidation under basal condition, but paradoxically enhances FA oxidation during forskolin- and contraction- mediated lipolysis. Moreover, PLIN5 partly protects muscle cells against lipid-induced lipotoxicity. In addition, we demonstrate that down-regulation of PLIN5 in skeletal muscle inhibits insulin-mediated glucose uptake under normal chow feeding condition, while paradoxically improving insulin sensitivity upon high-fat feeding. These data highlight a key role of PLIN5 in LD function, first by finely adjusting LD FA supply to mitochondrial oxidation, and second acting as a protective factor against lipotoxicity in skeletal muscle.

G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism.

Exercise-like effects by Estrogen-related receptor-gamma in muscle do not prevent insulin resistance in db/db mice.

Dissecting exercise-mimicking pathways that can replicate the benefits of exercise in obesity and diabetes may lead to promising treatments for metabolic disorders. Muscle estrogen-related receptor gamma (ERRγ) is induced by exercise, and when over-expressed in the skeletal muscle mimics exercise by stimulating glycolytic-to-oxidative myofiber switch, mitochondrial biogenesis and angiogenesis in lean mice. The objective of this study was to test whether muscle ERRγ in obese mice mitigates weight gain and insulin resistance. To do so, ERRγ was selectively over-expressed in the skeletal muscle of obese and diabetic db/db mice. Muscle ERRγ over-expression successfully triggered glycolytic-to-oxidative myofiber switch, increased functional mitochondrial content and boosted vascular supply in the db/db mice. Despite aerobic remodeling, ERRγ surprisingly failed to improve whole-body energy expenditure, block muscle accumulation of triglycerides, toxic diacylglycerols (DAG) and ceramides or suppress muscle PKCε sarcolemmal translocation in db/db mice. Consequently, muscle ERRγ did not mitigate impaired muscle insulin signaling or insulin resistance in these mice. In conclusion, obesity and diabetes in db/db mice are not amenable to selective ERRγ-directed programming of classic exercise-like effects in the skeletal muscle. Other biochemical pathways or integrated whole-body effects of exercise may be critical for resisting diabetes and obesity.

Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes.

Circulating natriuretic peptide (NP) levels are reduced in obesity and predict the risk of type 2 diabetes (T2D). Since skeletal muscle was recently shown as a key target tissue of NP, we aimed to investigate muscle NP receptor (NPR) expression in the context of obesity and T2D. Muscle NPRA correlated positively with whole-body insulin sensitivity in humans and was strikingly downregulated in obese subjects and recovered in response to diet-induced weight loss. In addition, muscle NP clearance receptor (NPRC) increased in individuals with impaired glucose tolerance and T2D. Similar results were found in obese diabetic mice. Although no acute effect of brain NP (BNP) on insulin sensitivity was observed in lean mice, chronic BNP infusion improved blood glucose control and insulin sensitivity in skeletal muscle of obese and diabetic mice. This occurred in parallel with a reduced lipotoxic pressure in skeletal muscle due to an upregulation of lipid oxidative capacity. In addition, chronic NP treatment in human primary myotubes increased lipid oxidation in a PGC1α-dependent manner and reduced palmitate-induced lipotoxicity. Collectively, our data show that activation of NPRA signaling in skeletal muscle is important for the maintenance of long-term insulin sensitivity and has the potential to treat obesity-related metabolic disorders.

Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals.

A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic subjects. Lipid trafficking and lipolysis were measured by pulse-chase assay with radiolabeled substrates in myotubes from non-obese/non-diabetic (lean), obese/non-diabetic (obese) and obese/diabetic (T2D) subjects. Lipolytic protein content and level of Akt phosphorylation were measured by Western blot. HSL was overexpressed by adenovirus-mediated gene delivery. Myotubes established from obese and T2D subjects had lower lipolysis (-30-40%) when compared to lean, using oleic acid as precursor. Similar observations were also seen for labelled glycerol. Incorporation of oleic acid into diacylglycerol (DAG) and free fatty acid (FFA) level was lower in T2D myotubes, and acetate incorporation into FFA and complex lipids was also lower in obese and/or T2D subjects. Both protein expression of HSL (but not ATGL) and changes in DAG during lipolysis were markedly lower in cells from obese and T2D when compared to lean subjects. Insulin-stimulated glycogen synthesis (-60%) and Akt phosphorylation (-90%) were lower in myotubes from T2D, however, overexpression of HSL in T2D myotubes did not rescue the diabetic phenotype. In conclusion, intrinsic defects in lipolysis and HSL expression co-exist with reduced insulin action in myotubes from obese T2D subjects. Despite reductions in intramyocellular lipolysis and HSL expression, overexpression of HSL did not rescue defects in insulin action in skeletal myotubes from obese T2D subjects.

Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis.

Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, promotes adipose tissue fibrosis. Ex vivo, lipopolysaccharide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFß1. Together, these results indicate that obesity and endotoxemia favor the development of adipose tissue fibrosis, a condition associated with insulin resistance, through immune cell Toll-like receptor 4.

Influence of lipolysis and fatty acid availability on fuel selection during exercise.

The aim of the present study was to investigate the influence of substrate availability on fuel selection during exercise. Eight endurance-trained male cyclists performed 90-min exercise at 70% of their maximal oxygen uptake in a cross-over design, either in rested condition (CON) or the day after 2-h exercise practised at 70% of maximal oxygen uptake (EX). Subjects were given a sucrose load (0.75 g kg(-1) body weight) 45 min after the beginning of the 90-min exercise test. Lipolysis was measured in subcutaneous abdominal adipose tissue (SCAT) by microdialysis and substrate oxidation by indirect calorimetry. Lipid oxidation increased during exercise and tended to decrease during sucrose ingestion in both conditions. Lipid oxidation was higher during the whole experimental period in the EX group (p = 0.004). Interestingly, fuel selection, assessed by the change in respiratory exchange ratio (RER), was increased in the EX session (p = 0.002). This was paralleled by a higher rate of SCAT lipolysis reflected by dialysate glycerol, plasma glycerol, and fatty acids (FA) levels (p < 0.001). Of note, we observed a significant relationship between whole-body fat oxidation and dialysate glycerol in both sessions (r (2) = 0.33, p = 0.02). In conclusion, this study highlights the limiting role of lipolysis and plasma FA availability to whole-body fat oxidation during exercise in endurance-trained subjects. This study shows that adipose tissue lipolysis is a determinant of fuel selection during exercise in healthy subjects.

Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects.

CONTEXT: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders. OBJECTIVES: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. DESIGN AND VOLUNTEERS: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. MAIN OUTCOME MEASURES: Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. RESULTS: Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive-lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G0/G1 switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). CONCLUSIONS: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity.

Dynamics of skeletal muscle lipid pools.

Intramyocellular triacylglycerol (IMTG) is emerging as an important energy fuel source during muscle contraction and are adaptively increased in response to exercise, without adverse physiological effects. Paradoxically, elevated IMTG content in obese and type 2 diabetics has been linked to insulin resistance, highlighting the importance of IMTG pools in physiology and pathology. Two separate views suggest that IMTG dynamics are determinant for skeletal muscle fat oxidation, and that disruption of IMTG dynamics facilitates the accumulation of lipotoxic intermediates such as diacylglycerols and ceramides that interfere with insulin signaling. Thus, understanding the factors that control IMTG dynamics is crucial. Here we discuss recent literature describing the regulation of IMTG pools with a particular emphasis on lipases and lipid droplet (LD)-associated proteins.

Enhanced glucose metabolism is preserved in cultured primary myotubes from obese donors in response to exercise training.

CONTEXT: It was suggested that human cultured primary myotubes retain the metabolic characteristics of their donor in vitro. OBJECTIVES: The aim of the present study was to investigate whether the metabolic responses to endurance training are also conserved in culture. DESIGN AND VOLUNTEERS: Middle-aged obese subjects completed an 8-week supervised aerobic exercise training program in which vastus lateralis muscle biopsies were collected before and after training. MAIN OUTCOME MEASURES: Anthropometric and blood parameters, as well as aerobic capacity, were assessed before and after training. Muscle biopsies were either used for Western blot analysis or digested to harvest myogenic progenitors that were differentiated into myotubes. Glucose oxidation, palmitate oxidation, and glycogen synthesis assays were performed on myotubes before and after training. Gene expression was assessed by real-time quantitative PCR. RESULTS: Our data indicate that in parallel of in vivo improvement of whole-body aerobic capacity and glucose metabolism, biopsy-derived primary myotubes showed similar patterns in vitro. Indeed, glucose oxidation, glycogen synthesis, and inhibition of palmitate oxidation by glucose were enhanced in myotubes after training. This was associated with consistent changes in the expression of metabolism-linked genes such as GLUT1, PDK4, and PDHA1. Interestingly, no difference in myogenic differentiation capacity was observed before and after training. CONCLUSION: Aerobic exercise training is associated with metabolic adaptations in vivo that are preserved in human cultured primary myotubes. It can be hypothesized that skeletal muscle microenvironmental changes induced by endurance training lead to metabolic imprinting on myogenic progenitor cells.

High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle.

Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cε membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P < .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (-37%, P < .05) and AS160 Thr642 (-47%, P <.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice.