Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Int J Mol Sci. 2019 Apr 25;20(8):2046. doi: 10.3390/ijms20082046.
Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect. Similarly, angiogenic capacity as measured by ex vivo capillary sprouting was significantly promoted with exercise. Together, these data demonstrate that exercise enhances scWAT vascularization and functional capacity for angiogenesis, and can prevent the detrimental effects of HFD. The improvement in these indices correlates with improvement of whole-body metabolism, suggesting that scWAT vascularization may be a potential therapeutic target for metabolic disease.
锻炼可以缓解糖尿病、心血管疾病和肥胖等慢性疾病；然而，控制这些疾病保护作用的分子机制尚不完全清楚。在这里，我们证明锻炼可以挽救代谢受损的高脂肪饮食（HFD）喂养的小鼠，并重新编程皮下白色脂肪组织（scWAT）。通过转录组谱分析，研究了 scWAT 中 HFD 基因表达变化，这些变化可以通过锻炼来挽救。血管生成相关的基因网络被确定为锻炼的主要靶点，这促使我们研究血管结构和内皮表型。研究发现，HFD 会导致 scWAT 中的血管密度受损，而锻炼则可以挽救这一缺陷。同样，通过体外毛细血管发芽测量的血管生成能力也显著得到锻炼的促进。总的来说，这些数据表明锻炼可以增强 scWAT 的血管生成和血管生成功能，并可以预防 HFD 的有害影响。这些指标的改善与全身代谢的改善相关，表明 scWAT 的血管生成可能是代谢疾病的潜在治疗靶点。
