A “metabolically unhealthy obesity” phenotype may be an important determinant of obesity-related blood vessel dysfunction.
Obesity and metabolic syndrome are directly associated with vascular (blood vessel) dysfunction since the perivascular adipose tissue (PVAT, fat tissue surrounding blood vessels) may affect vascular function and structure. However, the endothelium (outer layer of cells surrounding blood vessels) has an important role as a provider of adipocyte precursors as well as in the angiogenesis (blood vessel formation) process. For instance, PVAT may positively or negatively affect vascular function and structure depending on the leanness or fatness of each individual, respectively. Anti-inflammatory properties are observed both cases, but they are lost when someone has significant body fat.
The prevalence of vascular dysfunction is proportional to the accumulation of visceral fat (fat around the organs); a phenomenon known as a “metabolically unhealthy obesity” phenotype. On the other hand, a phenotype predominantly characterized by subcutaneous adipose tissue (STA, fat directly underneath the skin) is classified as “metabolically healthy obesity” because the STA may act against potentially toxic lipids. Therefore, the pattern of obesity plays a role in one’s cardiometabolic risk profile. The formation of new vascular networks is crucial in the process of the development of healthy adipose tissue since the endothelial cells tightly regulate it; this process of known as angiogenic-based adipose tissue differentiation. In this way, visceral adipose tissue (VAT) has a higher abundance of endothelial cells and increased vascular density, but also has more potent pro-inflammatory properties that cause metabolic and vascular complications related to obesity.
PVAT is an important regulator of vascular function with vasodilator, anti-contractile and anti-proliferative actions; it surrounds large, medium and small vascular beds. In the presence of obesity, PVAT increases production of inflammatory cytokines, such as IL-1, IL-6, and TNF-alpha, and impairs vascular function by also interfering with the release of nitric oxide (NO). Insulin resistance has a significant influence on vascular dysfunction as well, by regulating the PI3-kinase/Akt pathway and the MAP kinase cascade that contribute to NO and endothelin-1 system (ET-1) synthesis (ET-1 is associated with vasoconstriction, especially in the presence of hyperinsulinemia – excess insulin in the blood). PVAT is significantly associated with vascular insulin resistance by also increasing concentrations of inflammatory cytokines and free fatty acids (FFA). Adipokines such as adiponectin, apelin, and leptin play a role in vascular dysfunction. Some of the mechanisms of adipokines are associated with the signaling of phosphatidylinositol 3-kinase, mitogen-activated protein kinase, AMP-kinase, Akt and nitric oxide synthases, as well as with NO and ET-1.
On the other hand, gut hormones seem to be a factor in cardiometabolic prevention. Patients treated with glucagon-like peptide (GLP)-1 analogs (hormones that increase insulin secretion) have demonstrated a lower risk of cardiovascular disease compared to those who took a placebo. These results seem to be explained by the role of the GLP-1 gut peptide itself, rather than the minimal improvement of glucose control that was observed in GLP-1 patients. Obestatin appears to increase pancreatic beta cell (insulin synthesis and storage cell) proliferation and survival, improve glucose uptake and insulin sensitivity, and can inhibit lipolysis (the breakdown of lipids). It has also been shown that vascular function can be improved by increasing NO production.
Obesity-related vascular dysfunction is a condition characterized by a complex bidirectional interaction between the endothelium and PVAT, and this relationship is dependent on signaling molecules such as adipokines and gut hormones.
Written By: Vagner Raso