Abstract
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.
Highlights
Exercise is a powerful strategy to mitigate chronic diseases such as diabetes, cardiovascular diseases, and obesity
Examining the subcutaneous white adipose tissue (scWAT) phenotype, we found significant improvements in vascular integrity, density, and angiogenic potential in the high fat diet (HFD) exercised mice
We demonstrate that transcriptomic networks important in vascular expansion are negatively influenced by HFD and can be effectively reversed by chronic endurance exercise
Summary
Exercise is a powerful strategy to mitigate chronic diseases such as diabetes, cardiovascular diseases, and obesity. As these cardiometabolic diseases affect more than 25% of adults worldwide [1], finding molecular pathways that are important for disease prevention is paramount to improve outcomes and reduce the social and economic burden of disease. Exercise has proven to be an effective therapy for cardiometabolic diseases, the tissue-specific molecular mechanisms important for disease prevention, in conditions of Western eating habits (high fat diets), are still under investigation. WAT depots contain large lipid droplets that function as stIontr.aJ.gMeolr.eSpci.o2s0i1t9o, 2r0ie, xsFfOoRr PtErEigRlRyEcVeIrEiWdes, whereas BAT is metabolically active, full of mitoc2hoof n11dria, and high in expression of uncoupling protein 1 (Ucp1), which uncouples respiration from ATP prodsutocrtaiogne ,rreepsousilttoinrigesinfohretraitgplyrcoedriudcetsi,ownh. # p
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