PDF(Pubmed)
Abstract：
Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues\' thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by environmental factors like cold exposure or by pharmacology, share metabolic mechanisms that drive non-shivering thermogenesis. Understanding these two cell types requires advanced, yet broadly applicable in vitro models that reflect the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue, a tissue with \'beiging\' capacity in mice and humans. We show that adding a scaffold improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers, thus reflecting increased adipocyte maturity. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to classical 2D cultures, which was enhanced by β-adrenergic receptor stimulation correlating with elevated β-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes.
摘要：
脂肪组织,特别是米色和棕色的脂肪组织，在能量代谢中起着至关重要的作用。棕色脂肪组织的产热能力和白色脂肪组织中米色细胞的出现激发了人们对其代谢影响和治疗潜力的兴趣。棕色和米色脂肪细胞，被环境因素激活，如寒冷暴露或药理学，共享推动非颤抖产热的代谢机制。了解这两种细胞类型需要先进的，但广泛适用于反映脂肪组织复杂微环境和脉管系统的体外模型。在这里，我们介绍了来自腹股沟白色脂肪组织的基质血管微环境的小鼠血管化脂肪球体，在小鼠和人类中具有米色能力的组织。我们表明，添加支架可以改善血管发芽，促进球体生长，并上调成脂标记，因此反映了脂肪细胞成熟度的增加。通过RNA测序的转录分析揭示了我们的血管化脂肪球体中不同的代谢途径上调，与葡萄糖代谢相关的基因表达增加，脂质代谢，和产热。功能评估表明，与经典2D培养物相比，血管化脂肪球体的耗氧量增加。与β-肾上腺素能受体表达升高相关的β-肾上腺素能受体刺激增强。此外，用天然存在的脂肪因子刺激，FGF21诱导血管化脂肪球体中Ucp1mRNA表达。总之,血管化的腹股沟白色脂肪组织球体为研究基质血管微环境如何塑造脂肪细胞反应和影响米色脂肪细胞的激活产热提供了生理相关平台。
