Gut microbiota, a major contributor to human health, is influenced by physical activity and diet, and displays a functional cross-talk with skeletal muscle. Conversely, few data are available on the impact of hypoactivity, although sedentary lifestyles are widespread and associated with negative health and socio-economic impacts. The study aim was to determine the effect of Dry Immersion (DI), a severe hypoactivity model, on the human gut microbiota composition. Stool samples were collected from 14 healthy men before and after 5 days of DI to determine the gut microbiota taxonomic profiles by 16S metagenomic sequencing in strictly controlled dietary conditions. The α and β diversities indices were unchanged. However, the operational taxonomic units associated with the Clostridiales order and the Lachnospiraceae family, belonging to the Firmicutes phylum, were significantly increased after DI. Propionate, a short-chain fatty acid metabolized by skeletal muscle, was significantly reduced in post-DI stool samples. The finding that intestine bacteria are sensitive to hypoactivity raises questions about their impact and role in chronic sedentary lifestyles.

Propolis produced by honeybees, Apis mellifera, has been valued since ancient times as a remedy for different ailments for its broad medicinal properties. This wide range of biological activities may arise from the production of distinct propolis types within the hive, each serving specific functions and containing unique molecular compositions. In this study, we investigated the effects of four propolis types—masonry, sealing, brood-protection, and intruder-neutralizing—on hydrogen peroxide (H₂O₂)-induced oxidative injury in human skeletal muscle cells. Among these, only brood-protection propolis significantly prevented the H₂O₂-induced loss of cell viability. Bio-guided fractionation of this active propolis identified five major compounds: benzyl caffeate (BC), caffeic acid phenethyl ester (CAPE), cinnamyl caffeate (CC), prenyl caffeate (PC), and (E)-3-methyl-3-butenyl caffeate (MBC), all displaying stronger cytoprotective effects than their ferulate equivalents. We finally demonstrated that propolis extract and its active compounds reduced lipid peroxidation in post-mortem minced mouse skeletal muscle and compared their efficacy to other natural compounds. Chemical analysis of resins from neighboring flora suggested that black poplar (Populus nigra) buds are the primary botanical source of these caffeate derivatives. Collectively, these results highlight the functional diversity of hive propolis and its potential applications in food preservation as well as in complementary and preventive medicine.

Skeletal muscle has a remarkable plasticity, and its phenotype is strongly influenced by hormones, transcription factors, and physical activity. However, whether skeletal phenotype can be oriented or not during early embryonic stages has never been investigated. Here, we report that pyruvate as the only source of carbohydrate in the culture medium of mouse one cell stage embryo influenced the establishment of the muscular phenotype in adulthood. We found that pyruvate alone induced changes in the contractile phenotype of the skeletal muscle in a sexually dependent manner. For male mice, a switch to a more glycolytic phenotype was recorded, whereas, in females, the pyruvate induced a switch to a more oxidative phenotype. In addition, the influence of pyruvate on the contractile phenotypes was confirmed in two mouse models of muscle hypertrophy: the well-known myostatin deficient mouse (Mstn−/−) and a mouse carrying a specific deletion of p43, a mitochondrial triiodothyronine receptor. Finally, to understand the link between these adult phenotypes and the early embryonic period, we assessed the levels of two histone H3 post-translational modifications in presence of pyruvate alone just after the wave of chromatin reprogramming specific of the first cell cycle. We showed that H3K4 acetylation level was decreased in Mstn−/− 2-cell embryos, whereas no difference was found for H3K27 trimethylation level, whatever the genotype. These findings demonstrate for the first time that changes in the access of energy substrate during the very first embryonic stage can induce a precocious orientation of skeletal muscle phenotype in adulthood.

3D cell culture, using a variety of bioengineering techniques, enables muscle cells to be cultured in more structural and functional biomimetic conditions than 2D cell culture. Here, we tested the ability of an engineered 3D skeletal muscle model to recapitulate in vivo metabolic muscle response. First, C2C12 myoblasts in 3D cultures showed improved myogenesis, attested by increased differentiation time, myotube formation, and gene expression of differentiated muscle markers. At the functional level, the 3D muscle culture displayed contractile properties and proper mitochondrial respiration. Second, to highlight the interest of such system we used primary myoblasts derived from myostatin knockout ( Mstn ^−/− ) mice. When compared to control wild‐types 3D myotubes, 3D myotubes made from Mstn ^−/− myoblasts exhibit a hypertrophic phenotype associated with a decrease mitochondrial oxygen consumption, consistent with the skeletal muscle characteristics of Mstn ^−/− mice. Our findings show that 3D primary myotubes retain their in vivo phenotype in culture. This provides a useful framework for studying the underlying mechanisms of a various genetic muscle diseases, as well as for screening therapeutic drugs.

Myostatin plays crucial roles in negative regulation of muscle growth. Inactivation of the myostatin gene results in gross muscle hypertrophy. We observed that myostatin knock-out (myostatin-KO) mice are more aggressive than wild-type (WT) mice. Ghrelin is a hormone produced by cells of the gastrointestinal tract that activates cells in the brain and increases the drive to eat. The level of circulating ghrelin affects anxiety, stress, and aggression. Ghrelin controls expression of myostatin in disease-associated cachexia. Butyrylcholinesterase (BChE) is responsible for the deacylation of ghrelin. BChE knock-out mice show higher level of acylated ghrelin and are more aggressive than WT mice. De-acylation of ghrelin by BChE reduces aggression in mice. We hypothesized that the levels of expression of BChE, ghrelin and myostatin could explain the aggressive behavior of myostatin-myostatin-KO mice. Resident/intruder tests shows that male myostatin-KO mice are more aggressive than WT littermates. Female myostatin-KO mice show much higher spontaneous exercise than female WT and males of both genotypes. Behavioral tests (elevated plus maze and light/dark box) show that myostatin-KO mice present anxious behavior without any change in circulating corticosterone. Myostatin-KO mice have a lower acylated/unacylated ghrelin ratio. Female myostatin-KO mice show lower level of BChE activity compared with WT littermates. Comparison of staining for various neurotransmitter systems involved in behavior showed that the only region where there was a difference between WT and myostatin-KO mice was in the habenular complex which involved in regulation of behavior. Reduced ghrelin levels and loss of parvalbumin neurons of the habenular complex could partly explain the behavior of our model.