Aging-associated loss of adipose tissue in modification of vascular function and metabolism

Abstract Background Cardiovascular function is profoundly regulated by adipose tissue (AT) physiologically and pathologically. Adipose tissue is a highly active organ that their function, distribution and structure change in different organs and over a lifetime. Purpose We hypothesize that different AT compartments have distinct endocrine-like signaling which regulates cardiovascular (CV) function and the significant loss of specific AT during aging induces CV dysfunction. Our objective is to identify the contribution of AT in maintaining CV function during aging, the effects of known and so far unknown adipokines and their underlying molecular mechanisms in orchestrating vascular function and metabolic feature. Methods A unique genetically modified mouse model with adipocyte-MDM2 knockout (KO) is used in this study. KO mouse develops lipodystrophy over age and loses adipose tissue in their adulthood. We study vascular functional changes after loss of fat tissue, and after receiving transplanted subcutaneous fat from C57BJ/6 wild-type mice in KO mice, and study their changes in vascular signaling and metabolism. Results KO mice developed cardiovascular dysfunction by displaying significantly elevated systolic blood pressure and diastolic blood pressure. After transplantation of subcutaneous fat tissue, blood pressure and heart rate of KO mice were normalized. Arteries of KO mice showed stiffening remodeling and their aortic function was injured by a more pronounced contracting response to phenylephrine and declined relaxing response to acetylcholine. Their vascular function were improved in conditions with or without eNOS or COX inhibition, indicating that both eNOS or COX-dependent and non-dependent pathways are involved in beneficial effects of transplanted subcutaneous fat tissue on vascular function. Conclusions Subcutaneous fat tissue critically maintains normal vascular function at least partially via regulating endothelial eNOS and COX pathways.Figure 1 Figure 2