Title:Endothelial Dysfunction, Obesity and Insulin Resistance
Volume: 12
Issue: 3
Author(s): Dolores Prieto, Cristina Contreras and Ana Sanchez
Affiliation:
Keywords:
Endothelial dysfunction, endothelin-1, inflammation, nitric oxide, insulin resistance, obesity, oxidative stress, perivascular
adipose tissue.
Abstract: Obesity is a metabolic disorder of increasing prevalence worldwide and a risk factor for the development of insulin
resistance (IR), metabolic syndrome and type 2 diabetes. Obesity is related to endothelial dysfunction through indirect
mechanisms such as IR and the associated risk factors, and through direct mechanisms including the production of
proinflammatory adipokines and elevated levels of free fatty acids (FFAs) by adipose tissue. Both clinical and experimental
studies using genetic and diet-induced animal models of obesity have consistently shown impaired metabolic, agonistor
flow-induced vasodilatations correlated with the amount of visceral adipose tissue and improved by dietary interventions
and exercise. Compromised bioavailability of NO due to oxidative stress emerges as a main cause of endothelial
dysfunction in obesity. Inflamed adipose tissue due to hypoxia, and in particular perivascular adipose tissue (PVAT), secrete
larger amounts of reactive oxygen species (ROS) and adipokines that deteriorate NO signaling pathways. Abnormal
production and activity of the vasoconstrictor/proatherogenic peptide endothelin-1 (ET-1) is also a hallmark of the obesity-
associated endothelial dysfunction. Obesity, and in particular visceral obesity, is one of the main causes of IR, and the
pathogenic factors that induce endothelial dysfunction in the earlier stages of obesity will further deteriorate the insulin
signaling pathways in endothelial cells thus leading to blunted vasodilatation and abnormal capillary recruitment and substrate
delivery by insulin to the target tissues. The present review is an attempt to summarize the current knowledge and
the latest novel findings on the pathogenic mechanisms underlying endothelial dysfunction in obesity, in particular the local
contribution of oxidative stress and inflammatory response from PVAT, and its role in the obesity-associated cardiovascular
and metabolic complications.
