The role of adipose tissue in the regulation of endothelial function in type 2 diabetes: mechanisms and therapeutic implications
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The prevalence of obesity and diabetes is rising dramatically worldwide. Increased adiposity is associated with elevated cardiovascular risk factors, leading us to postulate a significant role for adipose in the regulation of cardiovascular function. Our goal is to understand the role of adipose in the regulation of endothelial function, and the effects of therapeutic interventions on ameliorating endothelial dysfunction by modulating adipose-derived factors in type 2 diabetes. First, we found that TNFα, an adipose-derived proinflammatory cytokine, plays a critical role in diabetes-associated endothelial dysfunction. As a natural anti-oxidant, resveratrol improves endothelial function by inhibiting TNFα and its downstream signaling. Second, adiponectin is an adipose-derived hormone. There is reciprocal regulation between adiponectin and TNFα in vasculature and adiponectin improves endothelial function. Third, as the hallmark cytokine of T-lymphocytes, IFNγ stimulates adipose inflammation, adipose/vascular oxidative stress, and macrophage accumulation in the adventitia of vasculature, and impairs endothelial function. Bariatric surgery is effective in ameliorating IFNγ-mediated adipose inflammation and endothelial dysfunction in type 2 diabetes. Therefore, adipose and adipose-derived factors are proposed to serve as promising therapeutic targets in the effort to manage type 2 diabetes and its vascular complications.
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