title: Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.
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. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) 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 perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.
authors: Department of Environmental Toxicology, University of California Davis, Davis, California, United States of America; Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, United States of America; Metabolism Institute, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Michele
authors: M
authors: La Merrill
authors: Department of Environmental Toxicology, University of California Davis, Davis, California, United States of America.
authors: Emma
authors: E
authors: Karey
authors: Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Erin
authors: E
authors: Moshier
authors: Metabolism Institute, Mount Sinai School of Medicine, New York, New York, United States of America; Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Claudia
authors: C
authors: Lindtner
authors: West Coast Metabolomic Center, University of California Davis, Davis, California, United States of America; Department of Nutrition, University of California Davis, Davis, California, United States of America.
authors: Michael R
authors: MR
authors: La Frano
authors: West Coast Metabolomic Center, University of California Davis, Davis, California, United States of America; Department of Nutrition, University of California Davis, Davis, California, United States of America; Obesity and Metabolism Research Unit, USDA-ARS-Western Human Nutrition Research Center, Davis, California, United States of America.
authors: John W
authors: JW
authors: Newman
authors: Metabolism Institute, Mount Sinai School of Medicine, New York, New York, United States of America; Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Christoph
authors: C
authors: Buettner
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D003080:Cold Temperature; D003634:DDT / Q000009:adverse effects*; D059305:Diet, High-Fat; D050171:Dyslipidemias / Q000209:etiology; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D007333:Insulin Resistance; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D023421:Models, Animal; D010575:Pesticides / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012737:Sex Factors
chemical_list: D010575:Pesticides; D003634:DDT