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Sex differences in diet and inhaled ozone (O3) induced metabolic impairment
Citation:
Kodavanti, U., V. Bass, M. Schladweiler, C. Gordon, K. Jarema, P. Phillips, A. Ledbetter, D. Miller, S. Snow, AND J. Richards. Sex differences in diet and inhaled ozone (O3) induced metabolic impairment. APS Meeting (Cardiovascular Renal and Metabolic Diseases: Physiology and Gender), Annapolis, MD, November 17 - 20, 2015.
Impact/Purpose:
Since metabolic processes of males and females are likely influenced by sex hormones, we examined differential susceptibility of male and female Brown Norway rats to high fructose versus high fat diet and the influence of acute ozone exposure on lung injury and metabolic impairment. We show that although dietary interventions did not have major sex specific effects, female BN rats are more susceptible to O3-induced pulmonary and metabolic effects.
Description:
APS 2015 abstract Sex differences in diet and inhaled ozone (O3) induced metabolic impairment U.P. Kodavanti1, V.L. Bass2, M.C. Schladweiler1, C.J. Gordon3, K.A. Jarema1, P. Phillips1, A.D. Ledbetter1, D.B. Miller4, S. Snow5, J.E. Richards1. 1 EPHD, NHEERL, USEPA, Research Triangle Park, NC. 2. SPH, UNC, Chapel Hill3. TAD, NHEERL, USEPA, Research Triangle Park, NC 4. CIT UNC, Chapel Hill5. ORISE, Oak Ridge, TNORISE, UNC SPH, Chapel Hill, NC, NHEERL, USEPA, Research Triangle Park, NCDiet and environmental stressors, including inhaled pollutants, have been implicated in the development and progression of metabolic diseases. Since metabolic processes of males and females are likely influenced by sex hormones, we hypothesized that high fat versus high fructose diet will produce differential metabolic impact in each sex, and that the injury induced by inhaled O3 as an environmental stressor, will be influenced by sex and dietary interventions. Male and female Brown Norway rats were fed either normal, high fructose or high fat diet beginning 1 month of age for 3 months. At 4th months they were exposed to air or O3 acutely (0.8 ppm) for 5 hours. The body fat composition and glucose tolerance (GT) were measured prior to O3 exposure. GT was also examined immediately after air or O3 exposure (n=10). Pulmonary toxicity and systemic metabolic changes were examined immediately after O3 exposure in a separate group of rats (n=10). Compared to males, female BN rats fed a normal diet had relatively greater body fat %, higher levels of serum triglycerides, cholesterol and glucose, and lower leptin and insulin. At baseline, male rats fed high fat diet had increased body fat but not females. GT did not differ between males and females but high fat diet induced a small degree of glucose intolerance in both males and females. High fructose but not high fat diet induced marked increases in circulating triglycerides in both males and females. High fat but not high fructose diet increased circulating leptin in both males and females. O3 exposure increased lung injury as determined by lavage fluid protein and albumin analysis in females fed all diets but only in high fat diet males. Both males and females had >10% of cells as eosinophils in the lung lavage fluid. No specific differences in BALF inflammatory cells were noted between air and O3 exposed rats of either sex on any diet, however, both diets decreased baseline levels of neutrophils in each sex. O3 induced glucose intolerance in each sex regardless of diet. O3 also increased circulating leptin (females>males) regardless of diet. No O3 effects occurred in circulating cholesterol or triglycerides in either sex. These data provide the evidence that although dietary interventions did not have major sex specific effects, female BN rats are more susceptible to O3-induced pulmonary and metabolic effects. (Does not reflect US EPA policy).