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Maternal air pollution exposure induces fetal neuroinflammation and predisposes offspring to obesity in aduthood in a sex-specific manner
Citation:
Bolton, J., S. Smith, N. Huff, M. Gilmour, W. Foster, R. Auten, AND S. Bilbo. Maternal air pollution exposure induces fetal neuroinflammation and predisposes offspring to obesity in aduthood in a sex-specific manner. FASEB JOURNAL. Federation of American Societies for Experimental Biology (FASEB), Bethesda, MD, 26(11):4743-54, (2012).
Impact/Purpose:
In summary, prenatal diesel exhaust exposure during pregnancy causes marked fetal brain cytokine responses, followed by an increased susceptibility to diet-induced weight gain, and metabolic and behavioral changes in adult offspring. Microglia primed by air pollutant-induced neuroinflammation during gestation may undergo exaggerated activation in response to a high-fat diet in adulthood, which may in turn mediate the changes in body weight regulation and metabolic function. We also demonstrated that fetal programming due to air pollution exposure in utero is sexually dimorphic, with more global detrimental effects in male offspring, both basally and in response to a high-fat diet. Further research is needed to determine the mechanism by which these marked sex differences in outcome are caused in response to the same prenatal and adult challenges. These findings may ultimately have implications for environmental policy regulations, as well as for social and clinical interventions.
Description:
Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pregnant mice were exposed to filtered air (FA) or diesel exhaust (DE) on embryonic days (E) 9-17. Prenatal DE induced a significant fetal brain cytokine response at E18 (46-390% over FA). As adults, offspring were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 6 weeks. Adult DE male offspring weighed 12% more and were 35% less active than FA male offspring at baseline, whereas there were no differences in females. Following HFD, DE males gained weight at the same rate as FA males, whereas DE females gained 340% more weight than FA females. DE-HFD males had 450% higher endpoint insulin levels than FA-HFD males, and all males on HFD showed decreased activity and increased anxiety, whereas females showed no differences. Finally, both DE males and females on HFD showed increased microglial activation (30-66%) within several brain regions. Thus, prenatal air pollution exposure can “program” offspring for increased susceptibility to diet-induced weight gain and neuroinflammation in adulthood in a sex-specific manner.