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. 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. 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.

中文翻译：

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涉及冬眠棕熊骨骼肌糖酵解的代谢重编程

在哺乳动物中，冬眠状态的特征在于生化调整，包括代谢率降低和主要燃料从碳水化合物氧化为脂质的转变。许多关于冬眠物种的研究报告说，在蛰伏期间肌肉中脂质氧化酶的水平和/或活性上调，同时糖酵解酶的下调。然而，其他研究提供了关于冬眠期间骨骼肌燃料利用调节的对比数据。熊只在中度低温下冬眠，但代谢率下降至基础代谢的 25%。为了深入了解冬眠熊骨骼肌中燃料代谢是如何调节的，我们检查了冬眠期间棕熊的股外侧肌蛋白质组和其他变化。我们表明熊肌肉代谢重组与抑制 ATP 周转一致。肌肉酶表达和活性的调节以及循环代谢物谱的调节突出了冬眠期间对脂质底物的偏好，尽管数据表明肌肉脂质氧化水平由于代谢率降低而降低。我们的数据还支持维持肌肉糖酵解，这可以通过肝脏糖异生和肌糖原储存的动员​​来推动。在冬眠期间，我们的数据还表明，熊肌肉中的碳水化合物代谢以及蛋白质的保留部分可以通过 n-3 多不饱和脂肪酸（如二十二碳六烯酸）的作用来控制。我们的工作表明冬眠熊骨骼肌的分子机制，这似乎与低代谢状态一致，可能有助于节省能量和蛋白质。维持糖酵解可以帮助维持肌肉功能，例如意外退出冬眠，这需要快速增加 ATP 产生以进行肌肉收缩。我们在此报告的关于在接近正常体温下冬眠的熊骨骼肌的分子数据代表了尽管处于萎缩状态但肌肉保存的特征。