Exploring the Role of Visceral Fat as a Negative Regulator of Vascular Function In Obesity

Abstract

Background and Objective. Obesity promotes endothelial dysfunction, a major contributor to the development of cardiovascular disease. Work from our lab and others previously showed robust impairment of arteries embedded within visceral adipose tissue as compared to those within subcutaneous adipose tissue. Here, our research is focused on obesity-induced changes in adipose tissue gene expression, and how it may negatively or positively impact the functioning of the vascular system within the tissue. Method. Visceral adipose tissue and subcutaneous adipose tissue were extracted from lean and diet-induced obese mice after 12-14 months on respective diets (normal chow and high fat, Western diet, respectively). RNA-seq was conducted to analyze the gene expression profiles, followed by quantitative polymerase chain reaction (qPCR) to validate specific gene expression changes. Finally, Western blots were performed to evaluate if changes were occurring at the protein level. Result. We identified obesity-induced changes in over two hundred eighty genes in visceral adipose tissue and more than two hundred twenty genes in subcutaneous adipose tissue when compared to visceral and subcutaneous adipose tissue from lean mice through RNA-seq analysis. We further identified genes that are over-expressed in subcutaneous adipose tissue but not in visceral adipose tissue, and vice versa, in response to diet-induced obesity. Changes in select genes were confirmed by polymerase chain reaction as well as Western blot. Discussion and Conclusions. These data may lead to important insights into the role of the identified adipose genes as they relate to the impact on arterial function. Future directions will involve approaches that delve deeper into the molecular and physiological understanding of the roles of specific adipose genes in influencing both adipose and endothelial function of the embedded arteries. We aim to ultimately determine if identified genes upregulated only in subcutaneous adipose tissue with obesity serve to spare the embedded vasculature from endothelial dysfunction and whether overexpressing such genes can restore visceral adipose artery endothelial function in obesity. This study was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under award number 2P20GM113125 (Ibra Fancher). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.