Robertson et al., 2023. AJP Endocrinology and Metabolism Data

Data for Robertson et al: <strong>"Turning up the heat”: Role of neurotrophic batokines in the postnatal maturation and remodelling of brown adipose tissue in deer mice</strong> Activation of brown adipose tissue (BAT) thermogenesis impacts energy balance and must be tightly regulated. Several neurotrophic factors, expressed in BAT of adult laboratory rodents, have been implicated in remodelling the sympathetic neural network to enhance thermogenesis (e.g., NGF, NRG4 and S100b). Here, we compare for the first time the relative roles of three neurotropic ‘batokines’ in establishing/remodelling innervation during postnatal development and adult cold stress. We used lab-reared <em>P. maniculatus,</em> which rely heavily on BAT-based thermogenesis for survival in the wild, beginning between postnatal days (P) 8 and 10. BAT sympathetic innervation was enhanced from P6-10, and exogenous NGF, NRG4, and S100b stimulated neurite outgrowth from P6 sympathetic neurons. Endogenous BAT protein stores and/or gene expression of NRG4, S100b, and calsyntenin-3ß (which regulates S100b secretion), remained high and constant during development. However, endogenous NGF was low and <em>ngf</em> mRNA was undetectable. Conditioned media (CM) from cultured P10 BAT slices stimulated neurite outgrowth from sympathetic neurons <em>in vitro</em> that was inhibited by antibodies against all three growth factors. P10 CM had significant amounts of secreted NRG4 and S100b protein, but not NGF. By contrast, BAT slices from cold-acclimated <em>adult</em>s released significant amounts of all three factors relative to thermoneutral controls. These data suggest that while neurotrophic batokines regulate sympathetic innervation <em>in vivo</em>, their relative contributions differ depending on life stage. They also provide novel insight into the regulation of BAT remodelling and BAT’s secretory role, which are both critical to our understanding of mammalian energy homeostasis.

Robertson等人的研究配套数据：**"升温"：神经营养棕色脂肪细胞因子（neurotrophic batokines）在鹿鼠棕色脂肪组织（brown adipose tissue, BAT）产后成熟与重塑中的作用**。棕色脂肪组织（BAT）产热激活会影响能量平衡，且必须受到严格调控。已在成年实验啮齿动物的BAT中表达的多种神经营养因子，被证实可重塑交感神经网络以增强产热功能（例如神经生长因子NGF、神经调节蛋白4 NRG4以及S100b）。本研究首次对比了三种神经营养棕色脂肪细胞因子在产后发育与成年冷应激阶段中，对交感神经支配的建立与重塑的相对作用。研究使用了实验室饲养的*P. maniculatus*，该物种在野外生存高度依赖基于BAT的产热功能，其产热依赖期始于产后第8至10日龄（postnatal days, P）。研究发现，BAT交感神经支配在P6-P10阶段得到增强，且外源性NGF、NRG4及S100b可促进P6交感神经元的神经突生长。发育过程中，内源性BAT蛋白储备以及NRG4、S100b和调节S100b分泌的calsyntenin-3ß的基因表达均维持在较高且稳定的水平。然而，内源性NGF含量较低，且*ngf* mRNA无法被检测到。体外（in vitro）实验中，培养的P10 BAT切片的条件培养基（conditioned media, CM）可刺激交感神经元的神经突生长，而针对上述三种生长因子的抗体可抑制这一效应。P10的条件培养基中含有大量分泌型NRG4和S100b蛋白，但不含NGF。与之相反，与热中性对照组相比，冷驯化成年个体的BAT切片可分泌上述三种因子。上述数据表明，尽管神经营养棕色脂肪细胞因子可在体内（in vivo）调控交感神经支配，但其相对贡献会因生命阶段不同而存在差异。本研究同时为BAT重塑的调控机制以及BAT的分泌功能提供了全新见解，这二者均是理解哺乳动物能量稳态（energy homeostasis）的关键所在。