Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle

Background: In mammals, the hibernating state is characterized by biochemical adjustments, which include metabolic rate depression and a shift in the primary fuel oxidized from carbohydrates to lipids. A number of studies of hibernating species report an upregulation of the levels and/or activity of lipid oxidizing enzymes in muscles during torpor, with a concomitant downregulation for glycolytic enzymes. However, other studies provide contrasting data about the regulation of fuel utilization in skeletal muscles during hibernation. Bears hibernate with only moderate hypothermia but with a drop in metabolic rate down to ~ 25% of basal metabolism. To gain insights into how fuel metabolism is regulated in hibernating bear skeletal muscles, we examined the vastus lateralis proteome and other changes elicited in brown bears during hibernation. Results: We show that bear muscle metabolic reorganization is in line with a suppression of ATP turnover. Regulation of muscle enzyme expression and activity, as well as of circulating metabolite profiles, highlighted a preference for lipid substrates during hibernation, although the data suggested that muscular lipid oxidation levels decreased due to metabolic rate depression. Our data also supported maintenance of muscle glycolysis that could be fuelled from liver gluconeogenesis and mobilization of muscle glycogen stores. During hibernation, our data also suggest that carbohydrate metabolism in bear muscle, as well as protein sparing, could be controlled, in part, by actions of n-3 polyunsaturated fatty acids like docosahexaenoic acid. Conclusions: Our work shows that molecular mechanisms in hibernating bear skeletal muscle, which appear consistent with a hypometabolic state, likely contribute to energy and protein savings. Maintenance of glycolysis could help to sustain muscle functionality for situations such as an unexpected exit from hibernation that would require a rapid increase in ATP production for muscle contraction. The molecular data we report here for skeletal muscles of bears hibernating at near normal body temperature represent a signature of muscle preservation despite atrophying conditions

Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells

Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders

Phénotypage fin de la composition corporelle : calibration et comparaison directe de huit méthodes chez la chèvre laitière

International audienceEight methods were compared to estimate dairy goat body composition, by calibrating against chemical composition measured post-mortem. The methods tested on 20 Alpine goats were body condition score (BCS), 3D imaging assessment of BCS or whole body scan, ultrasound, computer tomography (CT), adipose cell diameter, deuterium oxide dilution space (D2OS) and bioelectrical impedance spectroscopy. Regressions were tested between predictive variates and empty body composition. The best equations for estimation of lipid mass included body weight combined with i) perirenal adipose tissue mass and cell diameter (R² = 0.95), ii) volume of fatty tissues measured by CT (R² = 0.92), or iii) D2OS (R² = 0.91). The best equations for estimation of protein mass combined body weight with D2OS (R² = 0.97) or sternal BCS (R² = 0.95). Whole body 3D imaging method and ultrasound measurements were not satisfactory estimators of body composition (R² ≤ 0.40).Huit méthodes ont été comparées pour phénotyper la composition corporelle chez 20 chèvres laitières : la note d’état corporel (NEC), l’imagerie 3D pour estimer la NEC et reconstituer le corps entier, l’échographie, la tomodensitométrie (CT), le diamètre des adipocytes, l’espace de diffusion de l’eau deutérée (EDD2O) et l’impédancemétrie. Les différentes variables issues des méthodes testées ont été incluses dans des régressions linéaires pour déterminer la composition chimique du corps vide mesurée après abattage. Les équations les plus précises pour l’estimation de la masse de lipides combinent le poids vif et i) le poids total et le diamètre des adipocytes du tissu adipeux périrénal (R² = 0,95), ii) le volume des tissus gras mesuré par CT (R² = 0,92) ou iii) l’EDD2O (R² = 0,91). Les meilleures équations d’estimation de la masse de protéines incluent le poids vif et l’EDD2O (R² = 0,97) ou la NEC sternale (R² = 0,95). L’imagerie 3D corps entier et les mesures échographiques ne semblent pas être de bons estimateurs de la composition corporelle (R² ≤ 0.40)