Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.
Internal Medicine Research Unit, Worldwide Research, Development and Medical, Pfizer Inc, 1 Portland Street, Cambridge, MA, 02139, USA.
Sci Rep. 2020 Feb 11;10(1):2380. doi: 10.1038/s41598-020-59284-w.
Visceral white adipose tissue (vWAT) expands and undergoes extensive remodeling during diet-induced obesity. Much is known about the contribution of various stromal vascular cells to the remodeling process, but less is known of the changes that occur within the adipocyte as it becomes progressively dysfunctional. Here, we performed a transcriptome analysis of isolated vWAT adipocytes to assess global pathway changes occurring in response to a chronic high fat diet (HFD). The data demonstrate that the adipocyte responds to the HFD by adopting a fibroblast-like phenotype, characterized by enhanced expression of ECM, focal adhesion and cytoskeletal genes and suppression of many adipocyte programs most notably those associated with mitochondria. This study reveals that during obesity the adipocyte progressively becomes metabolically dysfunctional due to its acquisition of fibrogenic functions. We propose that mechano-responsive transcription factors such as MRTFA and SRF contribute to both upregulation of morphological genes as well as suppression of mitochondrial programs.
内脏白色脂肪组织 (vWAT) 在饮食诱导的肥胖中会扩张并经历广泛的重塑。人们已经了解了各种基质血管细胞对重塑过程的贡献，但对于脂肪细胞在逐渐功能失调时发生的变化知之甚少。在这里，我们对分离的 vWAT 脂肪细胞进行了转录组分析，以评估对慢性高脂肪饮食 (HFD) 发生的整体途径变化。数据表明，脂肪细胞通过采用成纤维细胞样表型来响应 HFD，其特征是细胞外基质 (ECM)、焦点粘连和细胞骨架基因的表达增强，以及许多脂肪细胞程序（尤其是与线粒体相关的程序）的抑制。这项研究表明，在肥胖过程中，脂肪细胞由于获得纤维生成功能而逐渐变得代谢功能失调。我们提出，机械反应转录因子（如 MRTFA 和 SRF）有助于上调形态发生基因和抑制线粒体程序。
