Arkansas Children's Nutrition Center, Little Rock, Arkansas.
Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.
Am J Physiol Endocrinol Metab. 2021 Jul 1;321(1):E63-E79. doi: 10.1152/ajpendo.00624.2020. Epub 2021 May 10.
Myoglobin (Mb) is a regulator of O bioavailability in type I muscle and heart, at least when tissue O levels drop. Mb also plays a role in regulating cellular nitric oxide (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, suggest 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 wild-type (WT) mice challenged with a high-fat diet (HFD, 45% of calories). In males ( = 10/genotype) and females ( = 9/genotype) tested at 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 with within-sex WT controls. At ∼18 and ∼19 wk of age, female Mb adiposity was ∼42%-48% higher versus WT females ( = 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. The roles of myoglobin remain to be elaborated. We address sexual dimorphism in terms of outcomes in response to the loss of myoglobin in knockout mice and perform, for the first time, a series of comprehensive metabolic studies under conditions in which fat is mobilized (high-fat diet, cold). The results highlight that myoglobin is not necessary and sufficient for maintaining oxidative metabolism and point to alternative roles for this protein in muscle and heart.
肌红蛋白 (Mb) 是 I 型肌肉和心脏中氧可用性的调节剂，至少在组织氧水平下降时是这样。Mb 还在调节细胞一氧化氮 (NO) 池方面发挥作用。长链脂肪酸和长链酰基辅酶 A 与 Mb 的牢固结合，以及 Mb 敲除 (KO) 小鼠心脏中葡萄糖代谢的增强，表明其在肌肉中间代谢和燃料选择中具有额外作用。为了评估这一假设，我们在接受高脂肪饮食 (HFD，占卡路里的 45%) 挑战的 Mb 敲除 (Mb) 和野生型 (WT) 小鼠中测量了能量消耗 (EE)、呼吸交换比 (RER)、体重增加和肥胖、葡萄糖耐量和胰岛素敏感性。在雄性 ( = 10/基因型) 和雌性 ( = 9/基因型) 中，在 5-6、11-12 和 17-18 周时进行测试，RER、EE 或食物摄入量不受基因型影响。与同性别 WT 对照相比，冷 (10°C，72 h) 时的 RER 和 EE 以及葡萄糖和胰岛素耐量并无差异。在大约 18 和 19 周龄时，雌性 Mb 的肥胖程度比 WT 雌性高约 42%-48% ( = 0.1)。整个比目鱼肌和比目鱼肌的转录组学分析显示，变化很少，唯一明显的例外是比目鱼肌转铁蛋白受体 (Tfrc) mRNA 下降 20%。Mb 中毛细血管指数显著增加，特别是在富含 Mb 的比目鱼肌和深部比目鱼肌中。结果表明，Mb 缺失对小鼠的整体葡萄糖稳态、EE、RER 或冷应激反应没有重大影响。然而，雌性 Mb 小鼠的肥胖程度更高表明 Mb KO 对脂肪储存和饲料效率有性别特异性影响。肌红蛋白的作用仍有待阐述。我们根据敲除小鼠中肌红蛋白缺失后的结果来探讨性别二态性，并首次在脂肪动员 (高脂肪饮食、寒冷) 的情况下进行一系列全面的代谢研究。结果强调了肌红蛋白对于维持氧化代谢不是必需和充分的，并指出了该蛋白在肌肉和心脏中的替代作用。
