A western diet-induced endothelial dysfunction in female rats. - GreenMedInfo Summary
Western diet triggers Toll-like receptor 4 (TLR4) signaling-induced endothelial dysfunction in female Wistar rats.
Am J Physiol Heart Circ Physiol. 2018 Sep 28. Epub 2018 Sep 28. PMID: 30265151
Overconsumption of a diet rich in fat and carbohydrates, called the western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17-weeks would develop endothelial dysfunction via endothelial Toll like receptor 4 (TLR4) signaling. Western diet-fed female rats exhibited dysregulation of metabolism revealing increases in body weight and abdominal fat, decreased expression of adiponectin in white adipose tissue, glucose intolerance, and impaired insulin sensitivity. Western diet exposure increased hepatic triglycerides and cholesterol alongside hepatic steatosis categorizing non-alcoholic fatty liver disease. Moreover, a western diet negatively affected vascular function revealing hypertension, impaired endothelium-dependent vasorelaxation, aortic remodeling, and increased reactive oxygen species (ROS) production. Aortic protein expression of TLR4 and its downstream proteins were markedly increased in the western diet group in association with elevated serum levels of free fatty acids. In vitro studies were conducted to test whether free fatty acids contribute to vascular ROS overproduction, via the TLR4 signaling pathway. Cultured endothelial cells were stimulated with palmitate in the presence of TAK-242, a TLR4 signaling inhibitor. Palmitate-induced over generation of ROS in endothelial cells was abolished in the presence of TAK-242. Our data show a western diet-induced endothelial dysfunction in female rats and suggests that endothelial TLR4 signaling may play a key role in abolishing female cardiovascular protection.