Systemic inflammation and peripheral organ injury after ozone exposure in diabetic rats receiving atherogenic diet
On this page:
Exposure to air pollutants is associated with increases in cardiometabolic diseases among susceptible individuals. While we have shown that ozone induces neuroendocrine stress-mediated homeostatic alterations in multiple organs, susceptible individuals with altered stress response may be predisposed to exacerbation of chronic diseases. The purpose was to determine the susceptibility of diabetic rats on control or atherogenic diets to acute ozone-induced systemic and peripheral organ changes in immunological and metabolic processes. Healthy, male Wistar and Wistar-derived Goto-Kakizaki (GK) rats, genetically predisposed to non-obese type 2 diabetes, received control or high-cholesterol atherogenic (HCA) diet beginning at 4 weeks of age for 12 weeks. Following the 12 week diet regimen, rats were exposed to air or 1 ppm ozone, 6h/day for 1 or 2 days and responses were analyzed at the end of each exposure. GK rats on the control diet were predisposed to hyperglycemia and glucose intolerance and increased body fat percentage relative to their Wistar counterparts; however, serum cholesterol and triglycerides levels were comparable between both strains. HCA diet increased circulating cholesterol, low-density lipoprotein, and insulin in both strains regardless of exposure. Increases in insulin levels found in GKs on the HCA diet were exacerbated after ozone exposure. Circulating lipase increased with HCA diet in both strains (Wistar>GK) and exposure groups. Likewise, circulating aspartate and alanine amino transferases increased in both strains receiving HCA diet with ozone exacerbating effects in GK rats, indicating liver injury. Circulating cytokines such as IFN-gamma, TNF-alpha, IL-6, and KC/GRO increased in both strains on HCA diet, and ozone, exacerbated these responses. Gene expression for metabolic markers was assessed using targeted Illumina sequencing in liver and muscle for both strains on control diet. Principle component analysis indicated strain differences in lipid and glucose metabolic markers and marked ozone effects in both liver and muscle, suggesting differential ozone impact in GK rats. These data provide insights into how ozone may exacerbate peripheral metabolic and systemic inflammatory changes in susceptible individuals on an unhealthy lipid-rich diet. (Does not reflect the US EPA policy).