Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring
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{"title"=>"Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring", "type"=>"journal", "authors"=>[{"first_name"=>"Michele", "last_name"=>"La Merrill", "scopus_author_id"=>"23501925800"}, {"first_name"=>"Emma", "last_name"=>"Karey", "scopus_author_id"=>"36925341400"}, {"first_name"=>"Erin", "last_name"=>"Moshier", "scopus_author_id"=>"6602306602"}, {"first_name"=>"Claudia", "last_name"=>"Lindtner", "scopus_author_id"=>"37661847300"}, {"first_name"=>"Michael R.", "last_name"=>"La Frano", "scopus_author_id"=>"55769433500"}, {"first_name"=>"John W.", "last_name"=>"Newman", "scopus_author_id"=>"7401659983"}, {"first_name"=>"Christoph", "last_name"=>"Buettner", "scopus_author_id"=>"6603742862"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84904988943", "doi"=>"10.1371/journal.pone.0103337", "pui"=>"373645981", "pmid"=>"25076055", "scopus"=>"2-s2.0-84904988943", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"bca9e63f-57f1-35fe-9b8c-5f6e3501cfa2", "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.", "link"=>"http://www.mendeley.com/research/perinatal-exposure-mice-pesticide-ddt-impairs-energy-expenditure-metabolism-adult-female-offspring", "reader_count"=>25, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>4, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>4, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>2, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>5, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>6}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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  • {"files"=>["https://ndownloader.figshare.com/files/1614521"], "description"=>"<p>(A) Female body mass at PND5 (n = 15 DDT- and n = 14 VEH- exposed litters). (B) Trunk blood glucose in PND5 females culled from litters >6 pups (n = 7 DDT- and n = 7 VEH- exposed litters). (C) Proportion of mice with vaginal opening as a function of age (n = 15 DDT- and n = 14 VEH- exposed litters). *p<0.05 DDT vs. vehicle controls. Data are represented as least squares (LS) means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt"], "article_id"=>1121995, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_perinatal_DDT_on_the_development_of_female_mice_/1121995", "title"=>"Effect of perinatal DDT on the development of female mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614522"], "description"=>"<p>Monthly (A) body mass (p = 0.05 at 2 months, p = 0.08 at 3 months), (B) percent adiposity (p = 0.05 at 3 months), (C) fat mass, (D) lean mass, and (E) food intake (A–E: n = 15 DDT- and n = 14 VEH- exposed litters). (F) Monthly core temperature (1 female/litter at 2 month time point, all females/litter thereafter, p = 0.07 at 2 months, age*DDT pi = 0.07). *p<0.05, **p<0.001, ***p<0.0001 DDT vs. vehicle controls. Data are represented as LS means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt"], "article_id"=>1121996, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_perinatal_DDT_on_body_composition_and_energy_balance_in_female_mice_/1121996", "title"=>"Effect of perinatal DDT on body composition and energy balance in female mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614524"], "description"=>"<p>(A) Oxygen consumption, (B) RER (period*DDT p<sub>interaction</sub><0.0001), (C) cumulative food intake, (D) energy expenditure, and (E) movement (over 5 day period and 4 female/treatment, 1 mouse/litter). (F) Core temperature (5 females/treatment, 1 female/litter). *p<0.05, **p<0.01, ***p<0.001 DDT vs. vehicle controls. Data are represented as LS means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt", "expenditure"], "article_id"=>1121998, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_perinatal_DDT_on_energy_expenditure_and_cold_tolerance_in_six_month_old_female_mice_/1121998", "title"=>"Effect of perinatal DDT on energy expenditure and cold tolerance in six month old female mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614525"], "description"=>"<p>(A) Weekly body mass (HFD*age pi<0.0001). (B) Percent adiposity in 8 month old mice. (C) Cumulative caloric intake over 12 weeks of HFD or LFD feeding. (D) Core temperature in 8 month old mice (DDT*HFD pi = 0.01). *p<0.05, **p<0.01, ***p<0.0001 A–B) LFD vs. HFD only; D) significance between groups indicated by bars. Data are represented as LS means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt", "hfd", "feeding", "mice", "veh"], "article_id"=>1121999, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_perinatal_DDT_and_adult_HFD_feeding_on_body_composition_and_energy_balance_in_female_mice_n_8202_8202_1_female_litter_in_7_VEH_and_8_DDT_litters_/1121999", "title"=>"Effects of perinatal DDT and adult HFD feeding on body composition and energy balance in female mice (n = 1 female/litter in 7 VEH and 8 DDT litters).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614526"], "description"=>"<p>(A) <i>Ppargc1a</i>- (DDT*HFD pi<0.01), (B) <i>Dio2</i>- (DDT*HFD pi<0.01), (C) <i>Ucp1</i>-, (D) <i>Glut4</i>- (DDT*HFD pi<0.05), (E) <i>Lpl</i>- (DDT*HFD pi<0.05), (F) <i>Pnpla</i>- (DDT*HFD pi<0.05), (G) <i>Cpt2-</i> (DDT*HFD pi<0.05), and (H) <i>Twist1</i>- (DDT*HFD pi<0.1) fold change (relative to LFD + VEH and adjusted by <i>Tbp</i>). *p<0.05, **p<0.01 significance between groups indicated by bars. Data are represented as LS means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt", "hfd", "feeding", "rna", "mice", "veh"], "article_id"=>1122000, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_perinatal_DDT_and_adult_HFD_feeding_on_RNA_expression_in_BAT_from_9_month_old_female_mice_n_8202_8202_1_female_litter_in_8_VEH_LFD_8_DDT_LFD_7_VEH_HFD_and_8_DDT_HFD_litters_/1122000", "title"=>"Effects of perinatal DDT and adult HFD feeding on RNA expression in BAT from 9 month old female mice (n = 1 female/litter in 8 VEH + LFD, 8 DDT + LFD, 7 VEH + HFD and 8 DDT + HFD litters).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614528"], "description"=>"<p>(A) Glucose tolerance test and resulting AUC (DDT*HFD pi = 0.08), (B) fasting insulin (DDT*HFD pi = 0.08) and (C) HOMA-IR (DDT*HFD pi = 0.07) in 8 month old mice. (D) Hepatic IRβ total, AKT 473 phosphorylation, AKT 308 phosphorylation, AKT total, GSK 3 phosphorylation, GSK 3 total, ERK phosphorylation, and ERK total fold change (relative to LFD + VEH and adjusted by HSC 70) as assessed by Western blot analysis (n = 1 female/litter in 7 VEH and 8 DDT litters) in 9 month old mice fed HFD. *p<0.05, **p<0.01, ***p<0.001 significance between groups indicated by bars. Data are represented as LS means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt", "hfd", "feeding", "glucose", "homeostasis", "mice", "veh"], "article_id"=>1122002, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_perinatal_DDT_and_adult_HFD_feeding_on_glucose_homeostasis_in_adult_female_mice_n_8202_8202_1_female_litter_in_8_VEH_LFD_8_DDT_LFD_7_VEH_HFD_and_8_DDT_HFD_litters_/1122002", "title"=>"Effects of perinatal DDT and adult HFD feeding on glucose homeostasis in adult female mice (n = 1 female/litter in 8 VEH + LFD, 8 DDT + LFD, 7 VEH + HFD and 8 DDT + HFD litters).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614530"], "description"=>"<p>Fasting- (A) total cholesterol (HFD*DDT pi = 0.02), (B) triglycerides (HFD*DDT pi = 0.16), and (C) NEFA in 8 month old mice. (D) Hepatic <i>Hmgcr</i>-, <i>Ldlr</i>-, and <i>Cyp7a1</i>- fold change (relative to LFD + VEH and adjusted by <i>Gusb</i>) in 9 month old female mice fed HFD. (E) Bile acid metabolites discriminated by DDT or VEH exposure (VIP>1). Inset: The PLS-DA Scores Plot demonstrates clear discriminatory separation of mice with or without perinatal DDT exposure along latent variable 1 (LV1). Symbols represent individual animals. Metabolite abbreviations followed by “(s)” indicate “screening” data without the benefit of authentic calibration standards. F) Hepatic FAS- (p = 0.14), ACC phosphorylation - (p = 0.13), ACC total-, ATPCL phosphorylation - (p = 0.07), ATPCL total-, and ATGL- (p = 0.22) fold change (relative to LFD + VEH and adjusted by HSC 70) in 9 month old female mice fed HFD. *p<0.05, **p<0.01, ***p<0.001 significance between groups indicated by bars. Data are represented as LS means + SEM.</p>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "perinatal", "ddt", "hfd", "feeding", "lipid", "homeostasis", "mice", "veh"], "article_id"=>1122004, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_perinatal_DDT_and_adult_HFD_feeding_on_lipid_homeostasis_in_adult_female_mice_n_8202_8202_1_female_litter_in_8_VEH_LFD_8_DDT_LFD_7_VEH_HFD_and_8_DDT_HFD_litters_/1122004", "title"=>"Effects of perinatal DDT and adult HFD feeding on lipid homeostasis in adult female mice (n = 1 female/litter in 8 VEH + LFD, 8 DDT + LFD, 7 VEH + HFD and 8 DDT + HFD litters).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-30 02:57:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1614538", "https://ndownloader.figshare.com/files/1614539", "https://ndownloader.figshare.com/files/1614540", "https://ndownloader.figshare.com/files/1614541", "https://ndownloader.figshare.com/files/1614542", "https://ndownloader.figshare.com/files/1614543", "https://ndownloader.figshare.com/files/1614544", "https://ndownloader.figshare.com/files/1614545", "https://ndownloader.figshare.com/files/1614546", "https://ndownloader.figshare.com/files/1614547", "https://ndownloader.figshare.com/files/1614548"], "description"=>"<div><p>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.</p></div>", "links"=>[], "tags"=>["physiology", "Endocrine physiology", "toxicology", "Endocrinology", "Endocrine-related substances", "Insulin resistance", "Diabetic endocrinology", "mice", "pesticide", "ddt", "impairs", "expenditure", "metabolism"], "article_id"=>1122012, "categories"=>["Biological Sciences"], "users"=>["Michele La merrill", "Emma Karey", "Erin Moshier", "Claudia Lindtner", "Michael R. La Frano", "John W. Newman", "Christoph Buettner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103337.s001", "https://dx.doi.org/10.1371/journal.pone.0103337.s002", "https://dx.doi.org/10.1371/journal.pone.0103337.s003", "https://dx.doi.org/10.1371/journal.pone.0103337.s004", "https://dx.doi.org/10.1371/journal.pone.0103337.s005", "https://dx.doi.org/10.1371/journal.pone.0103337.s006", "https://dx.doi.org/10.1371/journal.pone.0103337.s007", "https://dx.doi.org/10.1371/journal.pone.0103337.s008", "https://dx.doi.org/10.1371/journal.pone.0103337.s009", "https://dx.doi.org/10.1371/journal.pone.0103337.s010", "https://dx.doi.org/10.1371/journal.pone.0103337.s011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Perinatal_Exposure_of_Mice_to_the_Pesticide_DDT_Impairs_Energy_Expenditure_and_Metabolism_in_Adult_Female_Offspring_/1122012", "title"=>"Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-30 02:57:10"}

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Relative Metric

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