Abstract 10043: Arteriolar Function in Visceral Adipose Tissue is Impaired in Human Obesity
Background: Although clinical studies consistently link accumulation of intra-abdominal visceral fat to increased cardiovascular risk, disease mechanisms are largely unknown.
Methods and Results: In 27 severely obese subjects (age 41±10 yr, BMI 45 ±10 kg/m2) undergoing bariatric surgery, we intra-operatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes using RT-PCR, flow-cytometry, immunohistochemistry, and tissue culture. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μ m) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in arterioles intrinsic to visceral fat, even exhibiting paradoxical vasoconstriction in some vessels, compared to the subcutaneous depot (P<0.001 by ANOVA). Non-endothelium dependent responses to papaverine were similar. Endothelial nitric oxide synthase (eNOS) inhibition with Nω-nitro-L-arginine methyl ester (L-NAME) reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and higher capacity for basal and inducible cytokine production ex vivo.
Conclusions: Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play a significant role in shaping cardiovascular phenotypes in human obesity.
- © 2011 by American Heart Association, Inc.