Water deprivation induces a systemic pro-catabolic state that differentially affects oxidative and glycolytic skeletal muscles in male mice.

IF 2.2 3区 医学 Q3 PHYSIOLOGY
João da Cruz-Filho, Daniely Messias Costa, Tatiane Oliveira Santos, Raquel Prado da Silva, Hevely Catharine Anjos-Santos, Naima Jamile Santos Marciano, Roger Rodríguez-Gúzman, Ana Beatriz Henrique-Santos, João Eduardo Conceição Melo, Daniel Badauê-Passos, David Murphy, Andre Souza Mecawi, Danilo Lustrino
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Abstract

Dehydration, characterized by the loss of total body water and/or electrolytes due to diseases or inadequate fluid intake, is prevalent globally but often underestimated. Its contribution to long-term chronic diseases and sarcopenia is recognized, yet the mechanisms involved in systemic and muscle protein metabolism during dehydration remain unclear. This study investigated metabolic adaptations in a 36-hour water deprivation (WD) model of mice. Male C57BL/6 mice underwent 36-h WD or pair-feeding at rest, with assessments of motor skills along with biochemical, and metabolic parameters. Dehydration was confirmed by hypernatremia, body mass loss, hyporexia, and increased activity of vasopressinergic and oxytocinergic neurons compared to controls. These results were associated with liver mass loss, decreased glycaemia, and increased cholesterolemia. Additionally, increased VO2 and a decreased respiratory exchange ratio indicated reduced carbohydrate consumption and potentially increased protein use during dehydration. Thus, skeletal muscle protein metabolism was evaluated due to its high protein content. In the oxidative muscles of the WD group, total and proteasomal proteolysis increased, which was associated with decreased Akt-mediated intracellular signaling. Interestingly, there was an increase in fiber cross-sectional area, likely due to higher muscle water content caused by increased intracellular osmolality induced by protein catabolism products. Conversely, no changes were observed in protein turnover or water content in glycolytic muscles. These findings suggest that short-term WD imposes a pro-catabolic state, depleting protein content in skeletal muscle. However, skeletal muscle may respond differently to dehydration based on its phenotype and might adapt for a limited time.

缺水会诱导雄性小鼠出现系统性促代谢状态,这种状态会对氧化性和糖酵解性骨骼肌产生不同的影响。
脱水的特点是由于疾病或液体摄入不足导致体内总水分和/或电解质流失,在全球普遍存在,但往往被低估。脱水对长期慢性疾病和肌肉疏松症的影响已得到公认,但脱水时全身和肌肉蛋白质代谢的相关机制仍不清楚。本研究调查了小鼠在 36 小时缺水(WD)模型中的代谢适应情况。雄性 C57BL/6 小鼠在休息状态下接受了 36 小时的 WD 或配对喂养,并对运动技能、生化和代谢参数进行了评估。与对照组相比,高钠血症、体质量下降、厌食以及血管加压素能神经元和催产素能神经元活性增加证实了脱水。这些结果与肝脏质量下降、血糖降低和胆固醇血症增加有关。此外,VO2 的增加和呼吸交换比的降低表明脱水过程中碳水化合物的消耗减少,蛋白质的使用可能增加。因此,由于骨骼肌蛋白质含量高,我们对其蛋白质代谢进行了评估。在 WD 组的氧化肌肉中,总蛋白酶体和蛋白酶体蛋白分解增加,这与 Akt 介导的细胞内信号传导减少有关。有趣的是,纤维横截面积有所增加,这可能是由于蛋白质分解产物导致细胞内渗透压升高,从而使肌肉含水量增加。相反,在糖酵解肌肉中没有观察到蛋白质周转或含水量的变化。这些研究结果表明,短期 WD 强加了一种促进分解代谢的状态,消耗了骨骼肌中的蛋白质含量。然而,骨骼肌可能会根据其表型对脱水做出不同的反应,并可能在有限的时间内适应脱水。
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来源期刊
CiteScore
5.30
自引率
3.60%
发文量
145
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology publishes original investigations that illuminate normal or abnormal regulation and integration of physiological mechanisms at all levels of biological organization, ranging from molecules to humans, including clinical investigations. Major areas of emphasis include regulation in genetically modified animals; model organisms; development and tissue plasticity; neurohumoral control of circulation and hypertension; local control of circulation; cardiac and renal integration; thirst and volume, electrolyte homeostasis; glucose homeostasis and energy balance; appetite and obesity; inflammation and cytokines; integrative physiology of pregnancy-parturition-lactation; and thermoregulation and adaptations to exercise and environmental stress.
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