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

Data for Robertson et al:  
"Turning up the heat”: Role of neurotrophic batokines in the postnatal maturation and remodelling of brown adipose tissue in deer mice

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 P. maniculatus, 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 ngf mRNA was undetectable. Conditioned media (CM) from cultured P10 BAT slices stimulated neurite outgrowth from sympathetic neurons in vitro 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 adults released significant amounts of all three factors relative to thermoneutral controls. These data suggest that while neurotrophic batokines regulate sympathetic innervation in vivo, 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.

罗伯逊等人数据集：

“提升温度”：神经生长因子型蝙蝠激肽在鹿鼠出生后棕色脂肪组织成熟与重塑中的作用

棕色脂肪组织（BAT）的产热激活对能量平衡具有重大影响，其调控必须精确。多种神经生长因子已在成年实验鼠的BAT中发现，并被证明参与重塑交感神经网络以增强产热（例如，NGF、NRG4和S100b）。本研究首次比较了三种神经生长型‘蝙蝠激肽’在出生后发育和成年冷应激期间建立/重塑神经支配的相对作用。我们使用了实验室饲养的P. maniculatus，它们在野外生存高度依赖基于BAT的产热，这一过程始于出生后第8至10天。从出生后第6天至第10天，BAT的交感神经支配得到增强，外源性NGF、NRG4和S100b刺激了出生后第6天交感神经元的轴突生长。BAT的内源性蛋白储存和/或NRG4、S100b和calsyntenin-3β（调节S100b分泌的因子）的基因表达在发育过程中保持高水平且稳定。然而，内源性NGF水平较低，ngf mRNA无法检测到。培养的出生后第10天BAT切片的条件培养基（CM）在体外刺激了交感神经元的轴突生长，这一过程被针对所有三种生长因子的抗体所抑制。出生后第10天的CM含有显著量的分泌NRG4和S100b蛋白，但不含NGF。相比之下，适应寒冷的成年BAT切片释放了显著量的所有三种因子，相对于热中性对照组。这些数据表明，尽管神经生长因子型蝙蝠激肽在体内调节交感神经支配，但它们在不同生命阶段的相对贡献存在差异。这些数据还提供了关于BAT重塑和BAT分泌功能的调节机制的新见解，这两者对于理解哺乳动物能量稳态至关重要。