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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #313755
Title: Perinatal exposure to the pesticide DDT impairs energy expenditure and metabolism in adult female mice

Author
item LA MERRILL, MICHELLE - University Of California
item KAREY, EMMA - University Of California
item MOSHIER, ERIN - Mount Sinai School Of Medicine
item LINDTNER, CLAUDIA - Mount Sinai School Of Medicine
item LA FRANO, MICHAEL - University Of California
item Newman, John
item BUETTNER, CHRISTOPH - Mount Sinai School Of Medicine

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2014
Publication Date: 7/30/2014
Citation: La Merrill, M., Karey, E., Moshier, E., Lindtner, C., La Frano, M., Newman, J.W., Buettner, C. 2014. Perinatal exposure to the pesticide DDT impairs energy expenditure and metabolism in adult female mice. PLoS One. 9(7):e103337. doi: 10.1371/journal.pone.0103337.

Interpretive Summary: The insecticide dichlorodiphenyltrichloroethane (DDT) had been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Individuals exposed to elevated levels of DDT and its metabolites have an increased prevalence of diabetes and insulin resistance. We hypothesize that DDT exposure of mice during the preinatal period, i.e. the period of time before and after birth, would disrupt metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 (equivalent to a ~3rd week of human pregnancy) to postnatal day 5 (equivalent to a ~6 month human infant) and studied their metabolic phenotype at several ages up to nine months (equivalent to a 25 year old human). Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in the body fat of females. When challenged with a high fat diet for 12 weeks in adulthood, female offspring with perinatal DDT exposure developed glucose intolerance, hyperinsulinemia, dyslipidemia, altered bile acid metabolism and further thermogeneic impairment. Perinatal DDT exposure impaired RNA associated with substrate utilization and thermogenesis in the brown adipose of 9 month old female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis, carbohydrate-, and lipid- metabolism and may either cause metabolic syndrome in adult offspring or increase their susceptibility to this disorder.

Technical Abstract: Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring with perinatal DDT exposure developed glucose intolerance, hyperinsulinemia, dyslipidemia, altered bile acid metabolism and further impaired thermogenesis. Perinatal DDT exposure impaired RNA associated with substrate utilization and thermogenesis in the brown adipose of 9 month old female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis, carbohydrate-, and lipid- metabolism and may cause metabolic syndrome in adult offspring.