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THE INTERACTION OF MATERNAL HIGH-FAT DIET AND EXERCISE ON BRAIN MITOCHONDRIAL BIOENERGETICS IN RAT OFFSPRING AFTER OZONE EXPOSURE
Citation:
Valdez, M., D. Freeborn, A. Johnstone, Judy Schmid, U. Kodavanti, P. Phillips, C. Gordon, AND P. Kodavanti. THE INTERACTION OF MATERNAL HIGH-FAT DIET AND EXERCISE ON BRAIN MITOCHONDRIAL BIOENERGETICS IN RAT OFFSPRING AFTER OZONE EXPOSURE. Society of Toxicology, San Antonio, Texas, March 11 - 15, 2018.
Impact/Purpose:
Epidemiological studies indicate a negative impact of a sedentary lifestyle combined with increased consumption of high-fat diets on the increased incidence of obesity and related metabolic disorders. Such situations may impart a susceptibility to air pollutants, such as ozone, to the offspring. Current research of the adverse effects of ozone focus on peripheral morbidity, for this study we focused on central effects in the brain. The brain is unique with varieties of neurons and glial cells, each having specialized functions contributing to behavior, learning, and autonomic control. These functions have high energy requirements from mitochondrial bioenergetics, which are likely targets of chemical-induced neurotoxicity. We assayed the enzymatic rates of key mitochondrial enzymes (complex I, II and IV), in the frontal cortex and cerebellum in rat offspring of mothers maintained on control or high fat diets and with or without access to a running wheel. Our results indicate that ozone significantly affects brain mitochondrial bioenergetics and that a maternal diet and exercise regimen play a role in offspring’s susceptibility to ozone effects. Further understanding of these interactions may lead to designing lifestyle changes mothers can make that can mitigate the deleterious effects of ozone pollution in children.
Description:
Epidemiological studies indicate that a sedentary lifestyle combined with increased consumption of high-fat diets contributes to increased incidence of obesity and related metabolic disorders. These disorders during pregnancy may make offspring more susceptible to air pollutants. The brain is unique, with varieties of neurons and glial cells each having specialized functions contributing to behavior, learning, and autonomic control. These functions have high energy requirements from mitochondrial bioenergetics, a likely target of chemical-induced neurotoxicity. We have investigated whether maternal high-fat diet and exercise interact with effects of maternal O3 exposure on mitochondrial bioenergetics.in brains of offspring. For this study, female Long-Evans rats were fed either a control diet (CD), or a high-fat diet (HF; 60% calories in fat) for 6 weeks starting at 30 days of age and then bred. Gestational day (GD) 1 dams were housed with a running wheel (RW) or without (Sedentary: SED) until parturition. HF diet was terminated at postnatal day 35 and all offspring were fed CD thereafter. Adult offspring ~ 160 days (n-6/group) were exposed to air or O3 for 2 consecutive days (0.8 ppm, 4 hr/day), then rats were killed, brain regions were dissected on ice, snap-frozen and analyzed for complex I, complex II and complex IV enzymes in the frontal cortex (FC) and cerebellum (CB). Complex I enzyme activity (NADH dehydrogenase, EC 1.6.5.3) was similar across sex, brain region and O3 exposure group in offspring from CD mothers. O3 exposure increased complex I activity in the CB of male offspring from HF mothers but not when those mothers had access to a running wheel. Complex II enzyme activity (succinate dehydrogenase, EC 1.3.5.1) was elevated in the FC of male offspring from HF mothers, but not CD mothers, when exposed to O3. Within the CB of air-exposed male offspring from exercising CD mothers, there was an increase in complex II activity. Complex IV enzyme activity (cytochrome c oxidase, EC 1.9.3.1) was increased in the FC of males from O3-exposed HF mothers that were sedentary but decreased when mothers were active. O3 also increased complex IV activity in the CB of females from mothers maintained on HF. These results indicate that O3 significantly affects brain mitochondrial bioenergetics and that a maternal diet and exercise regimen play a role in offspring’s susceptibility to O3 effects. Further understanding of these interactions may lead to designing lifestyle changes mothers can make that can mitigate the deleterious effects of environmental stressors in children. (This abstract does not necessarily reflect USEPA policy).