L'horloge biologique du muscle

International audienceThe biological clock plays an essential role in the control of muscle activity, by dissociating temporally the metabolic functions of skeletal muscle. Exercise capacity also displays a circadian rhythm. Alterations in biological rhythm, as in shift workers, alter muscle function and are associated with the development of sarcopenia

Uncovering the Role of Glycogen in Brown Adipose Tissue

International audienceThe presence of glycogen in the brown adipose tissue (BAT) has been described 60 years ago. However, the role of this energetic storage in brown adipocytes has been long time underestimated. We have recently shown that during brown adipocyte differentiation in the embryo, glycogen accumulates and is degraded by glycophagy, a dynamic essential for lipid droplets biogenesis. Recent studies have shown that the storage and degradation of triglycerides in BAT are not essential for the activation of BAT in response to cold exposure in adults, and that glycogen can compensate for their absence. In this review, we report the recent advances related to the importance of glycogen in brown adipocytes

Du glycogène à la gouttelette lipidique

International audienceNo abstract availabl

Circadian control of metabolism and pathological consequences of clock perturbations.

International audienceMost organisms have developed an autonomous time-keeping system that generates self-sustained daily fluctuations in behavior and physiological processes. These biological clocks are reset every day by light to adjust physiology to the day/night cycle generated by the rotation of the Earth. Clocks present in organs involved in glucose and lipid metabolism such as the liver, muscle, adipose tissue and pancreas are also reset by feeding cues which permits the local integration of systemic and nutritional signals to switch fuel production and utilization according to the feeding/fasting cycle. However, derangements in this finely tuned system can be induced by extending light exposure, 24/7 food availability and altered food intake patterns, repeated jet-lag and shift-working, promoting metabolic imbalances ranging from body weight gain to the development of insulin resistance and liver diseases. Here, we review recent findings on the link between the clock and metabolic fluxes to maintain whole-body homeostasis, and what clock disruption in mice has revealed about the role of the clock in metabolic regulation

Endothelial cell specification in the somite is compromised in Pax3-positive progenitors of Foxc1/2 conditional mutants, with loss of forelimb myogenesis

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Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb

International audienceSignificance During embryonic development, multipotent stem cells progressively acquire specific cell fates. The somite is an embryological structure that gives rise to different mesodermal cell types, including skeletal muscle and vascular cells of blood vessels. We show by genetic manipulation that the Notch signaling pathway promotes a vascular cell-fate choice at the expense of skeletal muscle in the mouse somite. Pax3+ cells in the adjacent somites give rise to myogenic and endothelial cells in the limbs. Gain-of-function or inhibition of Notch signaling affects this cell-fate choice prior to the migration of these somite-derived cells into the limb. This embryological role of Notch is of potential therapeutic relevance to deriving stem cells for tissue repair

Itm2a is a Pax3 target gene, expressed at sites of skeletal muscle formation in vivo.

The paired-box homeodomain transcription factor Pax3 is a key regulator of the nervous system, neural crest and skeletal muscle development. Despite the important role of this transcription factor, very few direct target genes have been characterized. We show that Itm2a, which encodes a type 2 transmembrane protein, is a direct Pax3 target in vivo, by combining genetic approaches and in vivo chromatin immunoprecipitation assays. We have generated a conditional mutant allele for Itm2a, which is an imprinted gene, by flanking exons 2-4 with loxP sites and inserting an IRESnLacZ reporter in the 3' UTR of the gene. The LacZ reporter reproduces the expression profile of Itm2a, and allowed us to further characterize its expression at sites of myogenesis, in the dermomyotome and myotome of somites, and in limb buds, in the mouse embryo. We further show that Itm2a is not only expressed in adult muscle fibres but also in the satellite cells responsible for regeneration. Itm2a mutant mice are viable and fertile with no overt phenotype during skeletal muscle formation or regeneration. Potential compensatory mechanisms are discussed

MuscleJ: a high-content analysis method to study skeletal muscle with a new Fiji tool

International audienceSkeletal muscle has the capacity to adapt to environmental changes and regenerate upon injury. To study these processes, most experimental methods use quantification of parameters obtained from images of immunostained skeletal muscle. Muscle cross-sectional area, fiber typing, localization of nuclei within the muscle fiber, the number of vessels, and fiber-associated stem cells are used to assess muscle physiology. Manual quantification of these parameters is time consuming and only poorly reproducible. While current state-of-the-art software tools are unable to analyze all these parameters simultaneously, we have developed MuscleJ, a new bioinformatics tool to do so