Faculty, Doshisha University, Kyotanabe, Kyoto, Japan.
Organization for Research Initiatives and Development, Doshisha University, Kyotanabe, Kyoto, Japan.
Exp Physiol. 2021 Feb;106(2):463-474. doi: 10.1113/EP089114. Epub 2021 Jan 5.
What is the central question of this study? Exercise can stimulate brown adipose tissue (BAT) with subsequent increase in uncoupling protein 1 expression and mitochondrial biogenesis. In that case, do BAT-specific Hox genes modify BAT functioning and cause uncoupling protein expression changes due to exercise? What is the main finding and its importance? Exercise enhanced brown adipocyte markers, with significant upregulation of HoxA5 and downregulation of HoxC10 mRNA expression in rat BAT. HoxA5 and HoxC10 are thus likely to play distinct roles in exercise-induced changes in BAT markers during the early postnatal period. These findings provide new insight into the mechanisms underlying exercise-induced changes in BAT function.
Brown adipose tissue (BAT) recruitment is involved in increased energy expenditure associated with cold exposure and exercise training. We explored whether exercise training induced changes in expression levels of brown adipocyte-selective factors and Homeobox (Hox) genes during the post-weaning growth period of male Wistar rats. Relative to total body weight, BAT weights alone were lower in exercise-trained (EX) rats compared to sedentary control (SED) rats. mRNA expression of HoxA5 was higher and that of HoxC10 was lower in EX rats than in SED rats, accompanied by both higher citrate synthase activity and protein expression levels for uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor (PPAR) α, and PPARγ-coactivator (PGC)-1α. HoxA5 knockdown with siRNA reduced the expression of PR-domain containing 16 (Prdm16), cell death-inducing DNA fragmentation factor-α-like effector A (Cidea) gene, type 2 deiodinase mRNA, and PRDM16 protein. Comparatively, HoxC10 knockdown with siRNA enhanced mRNA expression of Prdm16, Pparα and Pgc1α and protein expression of UCP1, PPARα and PGC1α in brown adipocytes. The stimulation of brown adipocytes with isoproterenol, a β-adrenoceptor agonist, caused a phenomenon similar to the effect of exercise training on the genes tested: upregulation of HoxA5 mRNA, downregulation of HoxC10 mRNA, and increased protein expression for UCP1 and PGC1α. Collectively, HoxA5 and HoxC10 may have unique functions that contribute to modulating the expression of BAT-selective markers in BAT of juvenile rats during exercise training. The study findings regarding activation and recruitment of BAT during exercise training have implications for anti-obesity management.
本研究的核心问题是什么？运动可以刺激棕色脂肪组织（BAT），随后增加解偶联蛋白 1 的表达和线粒体生物发生。在这种情况下，BAT 特异性同源盒（Hox）基因是否会改变 BAT 的功能，并因运动导致解偶联蛋白表达的变化？主要发现及其重要性是什么？运动增强了棕色脂肪细胞标志物，大鼠 BAT 中 HoxA5 的 mRNA 表达显著上调，HoxC10 的 mRNA 表达下调。因此，HoxA5 和 HoxC10 可能在出生后早期运动诱导的 BAT 标志物变化中发挥不同的作用。这些发现为运动诱导的 BAT 功能变化的机制提供了新的见解。
棕色脂肪组织（BAT）的募集与冷暴露和运动训练引起的能量消耗增加有关。我们探讨了雄性 Wistar 大鼠在断奶后生长期间，运动训练是否会改变棕色脂肪细胞选择性因子和同源盒（Hox）基因的表达水平。与体重相比，运动训练（EX）大鼠的 BAT 重量单独降低，而久坐不动的对照（SED）大鼠则增加。与 SED 大鼠相比，EX 大鼠的 HoxA5 mRNA 表达更高，HoxC10 mRNA 表达更低，同时柠檬酸合酶活性和解偶联蛋白 1（UCP1）、过氧化物酶体增殖物激活受体（PPAR）α和过氧化物酶体增殖物激活受体γ共激活因子（PGC）-1α的蛋白表达水平也更高。用 siRNA 敲低 HoxA5 会降低 PR 结构域包含 16（Prdm16）、细胞死亡诱导 DNA 片段化因子-α样效应物 A（Cidea）基因、2 型脱碘酶 mRNA 和 PRDM16 蛋白的表达。相比之下，用 siRNA 敲低 HoxC10 会增强棕色脂肪细胞中 Prdm16、Pparα 和 Pgc1α 的 mRNA 表达，并增强 UCP1、PPARα 和 PGC1α 的蛋白表达。β-肾上腺素受体激动剂异丙肾上腺素刺激棕色脂肪细胞，导致与运动训练对所测试基因的影响类似的现象：HoxA5 mRNA 上调，HoxC10 mRNA 下调，UCP1 和 PGC1α 的蛋白表达增加。总之，HoxA5 和 HoxC10 可能具有独特的功能，有助于调节运动训练期间幼鼠 BAT 中 BAT 选择性标志物的表达。本研究关于运动训练期间 BAT 的激活和募集的发现，对肥胖管理具有重要意义。
