Citation:

Snow, S., A. Henriquez, A. Fisher, B. Vallanat, J. House, Mette C. Schladweiler, C. Wood, AND U. Kodavanti. Peripheral Metabolic Effects of Ozone Exposure in Healthy and Diabetic Rats on Normal or High-Cholesterol Diet. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 415(115427):1, (2021). https://doi.org/10.1016/j.taap.2021.115427

Impact/Purpose:

Air pollution health effects are exacerbated in individuals with underlying diabetes and those consuming unhealthy diets. In this study, we hypothesized that a high-cholesterol diet will lead to exacerbation of metabolic alterations in diabetic rats, owing to defects in insulin secretion and glucose metabolism. We show that diabetic rats were more sensitive to high cholesterol diet-induced obesity and glucose intolerance and adipose tissue atrophy when compared to healthy Wistar rats. Examining ozone effects in these rats we show that ozone induced changes in insulin homeostasis are exacerbated in diabetic rats leading to exacerbation of ozone effects in liver metabolic gene expression. Our data support the epidemiological findings showing exacerbation of air pollutant-induced health effects in humans with underlying obesity/diabetes.

Description:

Epidemiological studies show that individuals with underlying diabetes and diet-associated ailments are more susceptible than healthy individuals to adverse health effects of air pollution. Exposure to air pollutants can induce metabolic stress and increase cardiometabolic disease risk. Using male Wistar and Wistar-derived Goto-Kakizaki (GK) rats, which exhibit a non-obese type-2 diabetes phenotype, we investigated whether two key metabolic stressors, type-2 diabetes and a high-cholesterol atherogenic diet, exacerbate ozone-induced metabolic effects. Rats were fed a normal control diet (ND) or high-cholesterol diet (HCD) for 12 weeks and then exposed to filtered air or 1.0-ppm ozone (6 h/day) for 1 or 2 days. Metabolic responses were analyzed at the end of each day and after an 18-h recovery period following the 2-day exposure. In GK rats, baseline hyperglycemia and glucose intolerance were exacerbated by HCD vs. ND and by ozone vs. air. HCD also resulted in higher insulin in ozone-exposed GK rats and circulating lipase, aspartate transaminase, and alanine transaminase in all groups (Wistar>GK). Histopathological effects induced by HCD in the liver, which included macrovesicular vacuolation and hepatocellular necrosis, were more severe in Wistar vs. GK rats. Liver gene expression in Wistar and GK rats fed ND showed numerous strain differences, including evidence of increased lipid metabolizing activity and ozone-induced alterations in glucose and lipid transporters, specifically in GK rats. Collectively, these findings indicate that peripheral metabolic alterations induced by diabetes and high-cholesterol diet can enhance susceptibility to the metabolic effects of inhaled pollutants.

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