首页|Peripheral metabolic effects of ozone exposure in healthy and diabetic rats on normal or high -cholesterol diet

Peripheral metabolic effects of ozone exposure in healthy and diabetic rats on normal or high -cholesterol diet

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  • NSTL
  • Elsevier
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 (Wis-tar>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.

OzoneType-2 diabetes rat modelWestern high-cholesterol dietMetabolic responseAdipose tissueLiver

Snow, Samantha J.、Henriquez, Andres R.、Fisher, Anna、Vallanat, Beena、House, John S.、Schladweiler, Mette C.、Wood, Charles E.、Kodavanti, Urmila P.

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US EPA, Ctr Publ Hlth & Environm Assessment, Publ Hlth & Integrated Toxicol Div, Res Triangle Pk

US EPA, Oak Ridge Inst Sci & Educ Res Participat Program, Res Triangle Pk, NC 27711 USA

US EPA, Ctr Computat Toxicol & Exposure, Biomol & Computat Toxicol Div, Res Triangle Pk, NC 27711

NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA

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2021

10.1016/j.taap.2021.115427

Toxicology and Applied Pharmacology

Toxicology and Applied Pharmacology

SCI
ISSN：0041-008X
年,卷(期)：2021.415
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