Institute of Animal Breeding and Genetics, University of Veterinary Medicine, 1210, Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, 1090, Vienna, Austria; Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, 1210, Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, 1090, Vienna, Austria.
Mol Metab. 2020 Oct;40:101026. doi: 10.1016/j.molmet.2020.101026. Epub 2020 May 28.
Increasing energy expenditure through activation of brown adipose tissue (BAT) thermogenesis is an attractive approach to counteract obesity. It is therefore essential to understand the molecular mechanisms that control BAT functions. Until now several members of the Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway have been implicated as being relevant for BAT physiology. However, whether the STAT family member STAT5 is important for the thermogenic property of adipose tissues is unknown. Therefore, we have investigated the role of STAT5 in thermogenic fat in this paper.
We performed metabolic and molecular analyses using mice that harbor an adipocyte-specific deletion of Stat5a/b alleles.
We found that STAT5 is necessary for acute cold-induced temperature maintenance and the induction of lipid mobilization in BAT following β-adrenergic stimulation. Moreover, mitochondrial respiration of primary differentiated brown adipocytes lacking STAT5 was diminished. Increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic markers including uncoupling protein 1 (UCP1), while decreased stimulated lipolysis was linked to decreased protein kinase A (PKA) activity. Additionally, brown remodeling of white adipose tissue was diminished following chronic β-adrenergic stimulation, which was accompanied by a decrease in mitochondrial performance.
We conclude that STAT5 is essential for the functionality and the β-adrenergic responsiveness of thermogenic adipose tissue.
通过激活棕色脂肪组织（BAT）产热来增加能量消耗是对抗肥胖的一种有吸引力的方法。因此，了解控制 BAT 功能的分子机制至关重要。到目前为止，几种 Janus 激酶（JAK）-信号转导和转录激活因子（STAT）途径的成员已被认为与 BAT 生理学有关。然而，STAT 家族成员 STAT5 是否对脂肪组织的产热特性很重要尚不清楚。因此，我们在本文中研究了 STAT5 在产热脂肪中的作用。
我们使用脂肪细胞特异性缺失 Stat5a/b 等位基因的小鼠进行代谢和分子分析。
我们发现 STAT5 对于急性冷诱导的温度维持以及β-肾上腺素刺激后 BAT 中脂质动员的诱导是必需的。此外，缺乏 STAT5 的原代分化棕色脂肪细胞的线粒体呼吸作用减弱。STAT5 缺乏时对冷应激的敏感性增加与产热标志物的表达减少有关，包括解偶联蛋白 1（UCP1），而刺激脂肪分解减少与蛋白激酶 A（PKA）活性降低有关。此外，慢性β-肾上腺素刺激后白色脂肪组织的棕色重塑减少，伴随着线粒体功能下降。
我们得出结论，STAT5 对于产热脂肪组织的功能和β-肾上腺素反应性是必不可少的。
