Role of Inflammation in Vascular Disease-Related Perivascular Adipose Tissue Dysfunction

Perivascular adipose tissue (PVAT) is the connective tissue around most blood vessels throughout the body. It provides mechanical support and maintains vascular homeostasis in a paracrine/endocrine manner. Under physiological conditions, PVAT has anti-inflammatory effects, improves free fatty acid metabolism, and regulates vasodilation. In pathological conditions, PVAT is dysfunctional, secretes many anti-vasodilator factors, and participates in vascular inflammation through various cells and mediators; thus, it causes dysfunction involving vascular smooth muscle cells and endothelial cells. Inflammation is an important pathophysiological event in many vascular diseases, such as vascular aging, atherosclerosis, and hypertension. Therefore, the pro-inflammatory crosstalk between PVAT and blood vessels may comprise a novel therapeutic target for the prevention and treatment of vascular diseases. In this review, we summarize findings concerning PVAT function and inflammation in different pathophysiological backgrounds, focusing on the secretory functions of PVAT and the crosstalk between PVAT and vascular inflammation in terms of vascular aging, atherosclerosis, hypertension, diabetes mellitus, and other diseases. We also discuss anti-inflammatory treatment for potential vascular diseases involving PVAT.

Insulin Action, Glucose Homeostasis and Free Fatty Acid Metabolism: Insights From a Novel Model

Glucose and free fatty acids (FFA) are essential nutrients that are both partly regulated by insulin. Impaired insulin secretion and insulin resistance are hallmarks of aberrant glucose disposal, and type 2 diabetes (T2DM). In the current study, a novel model of FFA kinetics is proposed to estimate the role insulin action on FFA lipolysis and oxidation allowing estimation of adipose tissue insulin sensitivity (SIFFA). Twenty-five normal volunteers were recruited for the current study. To participate, volunteers had to be less than 40 years of age and have a body mass index (BMI) < 30 kg/m2, and be free of medical comorbidity. The proposed model of FFA kinetics was used to analyze the data derived from the insulin-modified FSIGT. Mean fractional standard deviations of the parameter estimates were all less than 20%. Standardized residuals of the fit of the model to the FFA temporal data were randomly distributed, with only one estimated point lying outside the 2-standard deviation range, suggesting an acceptable fit of the model to the FFA data. The current study describes a novel one-compartment non-linear model of FFA kinetics during an FSIGT that provides an FFA metabolism insulin sensitivity parameter (SIFFA). Furthermore, the models suggest a new role of glucose as the modulator of FFA disposal. Estimates of SIFFA confirmed previous findings that FFA metabolism is more sensitive to changes in insulin than glucose metabolism. Novel derived indices of insulin sensitivity of FFA (SIFFA) were correlated with minimal model indices. These associations suggest a cooperative rather than competitive interplay between the two primary nutrients (glucose and FFA) and allude to the FFA acting as the buffer, such that glucose homeostasis is maintained.