Myoglobin (Mb) is a regulator of O₂ bioavailability in type I muscle and heart, at least when tissue O₂ levels drop. Mb also plays a role in regulating cellular NO pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggests additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance and insulin sensitivity in Mb knockout (Mb^-/-) and wildtype (WT) mice challenged with a high fat diet (HFD, 45% of calories). In males (n=10/genotype) and females (n=9/genotype) aged 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10˚C, 72 h), and glucose and insulin tolerance, were not different compared to within-sex WT controls. At ~18 and ~19 wk of age, female Mb^-/- adiposity was ~42-48% higher vs. WT females (p=0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb^-/-, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole-body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb^-/- mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.

中文翻译：

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雄性和雌性肌红蛋白敲除小鼠的代谢生理学和骨骼肌表型

_{肌红蛋白 (Mb) 是 I 型肌肉和心脏中 O 2}生物利用度的调节剂，至少在组织 O ₂水平下降时是这样。Mb 还在调节细胞 NO 池中发挥作用。长链脂肪酸和长链酰基肉碱与 Mb 的强结合，以及增强的 Mb 敲除 (KO) 小鼠心脏中的葡萄糖代谢，表明在肌肉中间代谢和燃料选择中具有额外的作用。为了评估这一假设，我们测量了 Mb 敲除时的能量消耗 (EE)、呼吸交换率 (RER)、体重增加和肥胖、葡萄糖耐量和胰岛素敏感性 (Mb ^-/-) 和野生型 (WT) 小鼠受到高脂肪饮食 (HFD, 45% 的卡路里) 的挑战。在 5-6、11-12 和 17-18 周的男性（n=10/基因型）和女性（n=9/基因型）中，基因型对 RER、EE 或食物摄入没有影响。与性内 WT 对照相比，寒冷（10˚C，72 小时）期间的 RER 和 EE 以及葡萄糖和胰岛素耐受性没有差异。在约 18 周和约 19 周时，女性 Mb ^-/-肥胖比 WT 女性高约 42-48% (p=0.1)。转录组学分析（整个腓肠肌、比目鱼肌）显示几乎没有一致的变化，除了比目鱼肌转铁蛋白受体 (Tfrc) mRNA 下降 20% 的显着例外。以 Mb 为单位的毛细管指数显着增加^-/-，特别是在富含 Mb 的比目鱼肌和深腓肠肌中。结果表明，Mb 损失对小鼠的全身葡萄糖稳态、EE、RER 或对寒冷挑战的反应没有重大影响。然而，雌性 Mb ^-/-小鼠的肥胖程度较高表明 Mb KO 对脂肪储存和饲料效率具有性别特异性影响。