Recruitment of Muscle Genes as an Effect of Brown Adipose Tissue Ablation in Cold-Acclimated Brandt's Voles (Lasiopodomys brandtii).

Recruitment of Muscle Genes as an Effect of Brown Adipose Tissue Ablation in Cold-Acclimated Brandt's Voles (Lasiopodomys brandtii).
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DOI:
10.3390/ijms24010342
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发表时间:
2022-12-25
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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基于骨骼肌的非颤抖产热(NST)在鸟类和大型哺乳动物(不含棕色脂肪组织,BAT)的体温调节和维持中起着重要作用。然而,在野生小型哺乳动物中,基于肌肉的NST对体温调节的相对贡献并不清楚,因为它们已经进化出蝙蝠的专有生热器官。在这项研究中,我们研究了当Brandt田鼠(Lasiopoomys Brandtii)的BAT功能有条件地被最小化时,肌肉是否会成为NST的重要部位。我们用外科手术摘除肩胛间蝙蝠(iBAT,占总蝙蝠的52%~56%),并将其暴露在4℃的长期寒冷中28d。在整个冷驯化期间,iBAT消融的田鼠能够保持与假田鼠相同的NST和体温(~37.9℃)。冷习服组大鼠iBAT中解偶联蛋白1(UCP1)及其转录调控因子在蛋白质和mRNA水平的表达均高于温习服组。然而,除pGC-1α在BAT其他部位(包括肩下区、颈部和腋窝)外,这些产热相关标记物的蛋白和基因水平在温暖组和寒冷组之间没有差异,无论是假手术组还是iBAT消融组。在冷驯化过程中,iBAT损毁的田鼠的白色脂肪组织(WAT)中UCP1的表达高于假手术组。骨骼肌中肌磷脂(SLN)和肌浆内质网钙依赖性三磷酸腺苷(SERCA)的表达在冷热条件下高于温热环境,而磷蛋白(PLB)和磷酸化PLB(P-PLB)的表达无明显变化。此外,在寒冷条件下,iBAT消融的田鼠与假手术组相比增加了。此外,这些iBAT消融的田鼠经历了广泛的线粒体重塑和与线粒体代谢相关的关键组成部分的基因重塑。这些数据共同表明,在野生小型哺乳动物中,基于骨骼肌的生热作用可能补偿蝙蝠的损伤,并表明iBAT和骨骼肌两种形式的生热过程之间存在功能上的相互作用,以应对寒冷应激。
Skeletal muscle-based nonshivering thermogenesis (NST) plays an important role in the regulation and maintenance of body temperature in birds and large mammals, which do not contain brown adipose tissue (BAT). However, the relative contribution of muscle-based NST to thermoregulation is not clearly elucidated in wild small mammals, which have evolved an obligate thermogenic organ of BAT. In this study, we investigated whether muscle would become an important site of NST when BAT function is conditionally minimized in Brandt’s voles (Lasiopodomys brandtii). We surgically removed interscapular BAT (iBAT, which constitutes 52%~56% of total BAT) and exposed the voles to prolonged cold (4 °C) for 28 days. The iBAT-ablated voles were able to maintain the same levels of NST and body temperature (~37.9 °C) during the entire period of cold acclimation as sham voles. The expression of uncoupling protein 1 (UCP1) and its transcriptional regulators at both protein and mRNA levels in the iBAT of cold-acclimated voles was higher than that in the warm group. However, no difference was observed in the protein or mRNA levels of these thermogenesis-related markers except for PGC-1α in other sites of BAT (including infrascapular region, neck, and axilla) between warm and cold groups either in sham or iBAT-ablated voles. The iBAT-ablated voles showed higher UCP1 expression in white adipose tissue (WAT) than sham voles during cold acclimation. The expression of sarcolipin (SLN) and sarcoplasmic endoplasmic reticulum Ca2+-dependent adenosine triphosphatase (SERCA) in skeletal muscles was higher in cold than in warm, but no alteration in phospholamban (PLB) and phosphorylated-PLB (P-PLB) was observed. Additionally, there was increased in iBAT-ablated voles compared to that in the sham group in cold. Moreover, these iBAT-ablated voles underwent extensive remodeling of mitochondria and genes of key components related with mitochondrial metabolism. These data collectively indicate that recruitment of skeletal muscle-based thermogenesis may compensate for BAT impairment and suggest a functional interaction between the two forms of thermogenic processes of iBAT and skeletal muscle in wild small mammals for coping cold stress.
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