Myoglobin (Mb) regulates O₂ bioavailability in muscle and heart as partial pressure of O₂ (pO₂) drops with increased tissue workload. Globin proteins also modulate cellular NO pools, "scavenging" NO at higher pO₂ and converting NO₂^- to NO as pO₂ falls. Myoglobin binding of fatty acids may also signal a role in fat metabolism. Interestingly, Mb is expressed in brown adipose tissue (BAT), but its function is unknown. Herein, we present a new conceptual model that proposes links between BAT thermogenic activation, concurrently reduced pO₂, and NO pools regulated by deoxy/oxy-globin toggling and xanthine oxidoreductase (XOR). We describe the effect of Mb knockout (Mb^-/-) on BAT phenotype (lipid droplets, mitochondrial markers uncoupling protein 1 [UCP1] and cytochrome C oxidase 4 [Cox4], transcriptomics) in male and female mice fed a high fat diet (HFD, 45% of energy, ~13 wk), and examine Mb expression during brown adipocyte differentiation. Interscapular BAT weights did not differ by genotype, but there was a higher prevalence of mid-large sized droplets in Mb^-/-. COX4 protein expression was significantly reduced in Mb^-/- BAT, and a suite of metabolic/NO/stress/hypoxia transcripts were lower. All of these Mb^-/--associated differences were most apparent in females. The new conceptual model, and results derived from Mb^-/- mice, suggest a role for Mb in BAT metabolic regulation, in part through sexually dimorphic systems and NO signaling. This possibility requires further validation in light of significant mouse-to-mouse variability of BAT Mb mRNA and protein abundances in wildtype mice and lower expression relative to muscle and heart.

中文翻译：

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关于珠蛋白在棕色脂肪组织中的潜在作用：一种新的概念模型和肌红蛋白敲除小鼠的研究

肌红蛋白 (Mb) 调节肌肉和心脏中的 O _{2生物利用度，因为 O 2} (pO ₂ )的分压随着组织工作量的增加而下降。珠蛋白还调节细胞 NO 池，在 pO 2 较高时“清除” NO，并在_{pO 2}下降时将 NO ₂ ^-转化为 NO 。脂肪酸的肌红蛋白结合也可能表明在脂肪代谢中的作用。有趣的是，Mb 在棕色脂肪组织 (BAT) 中表达，但其功能未知。在此，我们提出了一个新的概念模型，该模型提出了 BAT 产热激活、同时降低 pO _{2之间的联系}，以及由脱氧/氧珠蛋白切换和黄嘌呤氧化还原酶 (XOR) 调节的 NO 池。我们描述了在喂食高脂肪饮食的雄性和雌性小鼠中，Mb 敲除 (Mb ^-/- ) 对 BAT 表型（脂滴、线粒体标记解偶联蛋白 1 [UCP1] 和细胞色素 C 氧化酶 4 [Cox4]、转录组学）的影响。 HFD，45% 的能量，~13 周），并检查棕色脂肪细胞分化过程中的 Mb 表达。^{肩胛间 BAT 重量没有因基因型而异，但在 Mb -/-}中中大型液滴的患病率较高。^{Mb -/-} BAT中的 COX4 蛋白表达显着降低，一组代谢/NO/压力/缺氧转录本较低。所有这些 Mb ^-/-相关的差异在女性中最为明显。新的概念模型和来自 Mb ^-/-小鼠的结果表明 Mb 在 BAT 代谢调节中的作用，部分通过性二态系统和 NO 信号传导。鉴于野生型小鼠中 BAT Mb mRNA 和蛋白质丰度的显着小鼠间变异性以及相对于肌肉和心脏的较低表达，这种可能性需要进一步验证。