Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites
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{"title"=>"Di-(2-ethylhexyl)-phthalate (DEHP) causes impaired adipocyte function and alters serum metabolites", "type"=>"journal", "authors"=>[{"first_name"=>"Nora", "last_name"=>"Klöting", "scopus_author_id"=>"8068435300"}, {"first_name"=>"Nico", "last_name"=>"Hesselbarth", "scopus_author_id"=>"56373394500"}, {"first_name"=>"Martin", "last_name"=>"Gericke", "scopus_author_id"=>"56450476200"}, {"first_name"=>"Anne", "last_name"=>"Kunath", "scopus_author_id"=>"56188710100"}, {"first_name"=>"Ronald", "last_name"=>"Biemann", "scopus_author_id"=>"54408082400"}, {"first_name"=>"Rima", "last_name"=>"Chakaroun", "scopus_author_id"=>"54408057900"}, {"first_name"=>"Joanna", "last_name"=>"Kosacka", "scopus_author_id"=>"8621211200"}, {"first_name"=>"Peter", "last_name"=>"Kovacs", "scopus_author_id"=>"55728560000"}, {"first_name"=>"Matthias", "last_name"=>"Kern", "scopus_author_id"=>"55682653985"}, {"first_name"=>"Michael", "last_name"=>"Stumvoll", "scopus_author_id"=>"56965303600"}, {"first_name"=>"Bernd", "last_name"=>"Fischer", "scopus_author_id"=>"56653015500"}, {"first_name"=>"Ulrike", "last_name"=>"Rolle-Kampczyk", "scopus_author_id"=>"6701639305"}, {"first_name"=>"Ralph", "last_name"=>"Feltens", "scopus_author_id"=>"36950523100"}, {"first_name"=>"Wolfgang", "last_name"=>"Otto", "scopus_author_id"=>"57075996900"}, {"first_name"=>"Dirk K.", "last_name"=>"Wissenbach", "scopus_author_id"=>"8836335200"}, {"first_name"=>"Martin", "last_name"=>"Von Bergen", "scopus_author_id"=>"6603254363"}, {"first_name"=>"Matthias", "last_name"=>"Blüher", "scopus_author_id"=>"6602576090"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84955480740", "pui"=>"607883940", "sgr"=>"84955480740", "pmid"=>"26630026", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0143190"}, "id"=>"3fb33dc8-1301-3b69-9cf9-006feb6ccc4f", "abstract"=>"Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated. We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level.", "link"=>"http://www.mendeley.com/research/di2ethylhexylphthalate-dehp-causes-impaired-adipocyte-function-alters-serum-metabolites", "reader_count"=>25, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>3, "Student > Ph. D. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2597331"], "description"=>"<p><b>(A)</b> Body weight gain during treatment with DEHP <b>(B)</b> Insulin tolerance test of 129S6 mice (N = 8 controls, N = 8 DEHP treatment) after 6 weeks of DEHP intake <b>(C)</b> fat mass and <b>(D)</b> lean mass as percent of body weight was determined in awake female mice by using nuclear magnetic resonance technology with EchoMRI700 instrument (Echo Medical Systems, Houston, TX, USA) at the end of observation period (10 weeks). Data are presented as percentage of total body fat and lean mass from body weight. Results are expressed as means ± SE from at least 5 female animals per treatment group. <b>(E)</b> Food intake per animal, day and body weight calculated from food intake and body weight measurements in weeks 5 and 6 of treatment. <b>(F)</b> ipGTT was performed on 4-h-fasted after 8 weeks of DEHP treatment in female mice. Results are expressed as means ± SE from at least 5 female animals per treatment group. <b>(G)</b> Serum adiponectin and <b>(H)</b> estrogen concentrations were analyzed at the end of observation period (10 weeks) in female mice (n = 5 per treatment group). Data are presented as mean ± SE from at least 5 female animals per treatment group. <b>(I)</b> Western Blot quantification of estrogen receptor protein expression (Esr1), <b>(J)</b> glucocorticoid receptor (Glur), Adiponectin <b>(K)</b> and Ppary <b>(L)</b> in subcutaneous (SC) and visceral adipose tissue of female 129S6 mice (at least n = 3 per experimental group). <b>(M)</b> Representative images in adipose tissue of control and DEHP treated mice. Equal protein loading was verified using mouse anti-D-glyceraldehyde-3-phosphate dehydrogenase (Gapdh) antibody. The different degrees of significance (t-test with Welch correction) were indicated as follows in the graphs. *p<0.05; ** p< 0.01.</p>", "links"=>[], "tags"=>["DEHP exposure causes", "DEHP treatment causes", "insulin tolerance tests", "insulin sensitivity", "DEHP treatment", "triglyceride serum concentrations", "glucose", "DEHP treatment increases", "129 S 6 mice", "Insulin tolerance", "Causes Impaired Adipocyte Function", "Adipose tissue", "adipose tissue Pparg"], "article_id"=>1616487, "categories"=>["Biological Sciences"], "users"=>["Nora Klöting", "Nico Hesselbarth", "Martin Gericke", "Anne Kunath", "Ronald Biemann", "Rima Chakaroun", "Joanna Kosacka", "Peter Kovacs", "Matthias Kern", "Michael Stumvoll", "Bernd Fischer", "Ulrike Rolle-Kampczyk", "Ralph Feltens", "Wolfgang Otto", "Dirk K. Wissenbach", "Martin von Bergen", "Matthias Blüher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0143190.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_studies_of_129S6_mice_/1616487", "title"=>"<i>In vivo</i> studies of 129S6 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 03:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2597333"], "description"=>"<p><b>(A)</b> Volcano plot (fold-change vs significance) of the comparison between metabolites of the exposed group and the control group of female 129S6 mice. The color code for different analyte classes is shown. <b>(B)</b> Box-and-whisker plot of selected metabolites. Medians, interquartile ranges (boxes) as well as minimal and maximal values (whiskers) are indicated. Significant differences between metabolites are marked with: *p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.</p>", "links"=>[], "tags"=>["DEHP exposure causes", "DEHP treatment causes", "insulin tolerance tests", "insulin sensitivity", "DEHP treatment", "triglyceride serum concentrations", "glucose", "DEHP treatment increases", "129 S 6 mice", "Insulin tolerance", "Causes Impaired Adipocyte Function", "Adipose tissue", "adipose tissue Pparg"], "article_id"=>1616489, "categories"=>["Biological Sciences"], "users"=>["Nora Klöting", "Nico Hesselbarth", "Martin Gericke", "Anne Kunath", "Ronald Biemann", "Rima Chakaroun", "Joanna Kosacka", "Peter Kovacs", "Matthias Kern", "Michael Stumvoll", "Bernd Fischer", "Ulrike Rolle-Kampczyk", "Ralph Feltens", "Wolfgang Otto", "Dirk K. Wissenbach", "Martin von Bergen", "Matthias Blüher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0143190.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_metabolome_profile_indicates_significant_changes_in_lipids_and_carnitines_/1616489", "title"=>"Serum metabolome profile indicates significant changes in lipids and carnitines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 03:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2597335"], "description"=>"<p><b>(A)</b> BrdU incorporation in 3T3-L1 adipocytes. BrdU incorporation was assessed in 3T3-L1 preadipocytes grown on glass coverslips. Cells were induced to differentiate for 24 h, and then incubated with 10 μM BrdU for 3 h. <b>(B)</b> BrdU staining- BrdU-labeled cells were visualized using an anti-BrdU antibody and an Alexa Fluor<sup>®</sup> 488 anti-mouse antibody <b>(C)</b> Triglyceride content in mature 3T3-L1 cells <b>(D)</b> Oil Red O staining of 3T3-L1 adipocytes reveals reduced number of lipid droplet containing cells. 3T3-L1 cells were stained 8 days after induction (magnification 200x). <b>(E)</b> Basal and insulin stimulated uptake of 2-deoxy-D [<sup>14</sup>C] glucose was significantly increased in 3T3-L1 cells treated with DEHP. <b>(F)</b> Palmitic acid uptake in mature adipocytes with and without DEHP treatment. ** p<0.01, *** p<0.001.</p>", "links"=>[], "tags"=>["DEHP exposure causes", "DEHP treatment causes", "insulin tolerance tests", "insulin sensitivity", "DEHP treatment", "triglyceride serum concentrations", "glucose", "DEHP treatment increases", "129 S 6 mice", "Insulin tolerance", "Causes Impaired Adipocyte Function", "Adipose tissue", "adipose tissue Pparg"], "article_id"=>1616491, "categories"=>["Biological Sciences"], "users"=>["Nora Klöting", "Nico Hesselbarth", "Martin Gericke", "Anne Kunath", "Ronald Biemann", "Rima Chakaroun", "Joanna Kosacka", "Peter Kovacs", "Matthias Kern", "Michael Stumvoll", "Bernd Fischer", "Ulrike Rolle-Kampczyk", "Ralph Feltens", "Wolfgang Otto", "Dirk K. Wissenbach", "Martin von Bergen", "Matthias Blüher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0143190.g003", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEHP_treatment_causes_enhanced_proliferation_rate_reduces_lipid_content_altered_uptake_of_2_deoxy_D_14_C_glucose_and_similar_palmitic_acid_uptake_into_3T3_L1_adipocytes_/1616491", "title"=>"DEHP treatment causes enhanced proliferation rate, reduces lipid content, altered uptake of 2-deoxy-D [<sup>14</sup>C] glucose and similar palmitic acid uptake into 3T3-L1 adipocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 03:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2597336"], "description"=>"<p>mRNA expression of key genes <b>(A)</b> in adipose tissue function was performed using RT-PCR. <b>(B)</b> Western Blot analysis of adiponectin and phospho-phosphoinositol 3-kinase <i>(Pi3-k)</i> and quantification of protein level. * p<0.05, ** p<0.01</p>", "links"=>[], "tags"=>["DEHP exposure causes", "DEHP treatment causes", "insulin tolerance tests", "insulin sensitivity", "DEHP treatment", "triglyceride serum concentrations", "glucose", "DEHP treatment increases", "129 S 6 mice", "Insulin tolerance", "Causes Impaired Adipocyte Function", "Adipose tissue", "adipose tissue Pparg"], "article_id"=>1616492, "categories"=>["Biological Sciences"], "users"=>["Nora Klöting", "Nico Hesselbarth", "Martin Gericke", "Anne Kunath", "Ronald Biemann", "Rima Chakaroun", "Joanna Kosacka", "Peter Kovacs", "Matthias Kern", "Michael Stumvoll", "Bernd Fischer", "Ulrike Rolle-Kampczyk", "Ralph Feltens", "Wolfgang Otto", "Dirk K. Wissenbach", "Martin von Bergen", "Matthias Blüher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0143190.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_level_and_protein_expression_in_mature_3T3_L1_adipocytes_/1616492", "title"=>"mRNA level and protein expression in mature 3T3-L1 adipocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-02 03:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2597337"], "description"=>"<p>Data obtained after 10 weeks of treatment are given as mean ± SEM.</p>", "links"=>[], "tags"=>["DEHP exposure causes", "DEHP treatment causes", "insulin tolerance tests", "insulin sensitivity", "DEHP treatment", "triglyceride serum concentrations", "glucose", "DEHP treatment increases", "129 S 6 mice", "Insulin tolerance", "Causes Impaired Adipocyte Function", "Adipose tissue", "adipose tissue Pparg"], "article_id"=>1616493, "categories"=>["Biological Sciences"], "users"=>["Nora Klöting", "Nico Hesselbarth", "Martin Gericke", "Anne Kunath", "Ronald Biemann", "Rima Chakaroun", "Joanna Kosacka", "Peter Kovacs", "Matthias Kern", "Michael Stumvoll", "Bernd Fischer", "Ulrike Rolle-Kampczyk", "Ralph Feltens", "Wolfgang Otto", "Dirk K. Wissenbach", "Martin von Bergen", "Matthias Blüher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0143190.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotype_of_DEHP_treated_female_129S6_and_control_animals_n_5_per_group_/1616493", "title"=>"Phenotype of DEHP treated female 129S6 and control animals (n = 5 per group).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-12-02 03:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2597338", "https://ndownloader.figshare.com/files/2597339"], "description"=>"<div><p>Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice <i>in vivo</i>. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated. We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. <i>In vitro</i>, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level.</p></div>", "links"=>[], "tags"=>["DEHP exposure causes", "DEHP treatment causes", "insulin tolerance tests", "insulin sensitivity", "DEHP treatment", "triglyceride serum concentrations", "glucose", "DEHP treatment increases", "129 S 6 mice", "Insulin tolerance", "Causes Impaired Adipocyte Function", "Adipose tissue", "adipose tissue Pparg"], "article_id"=>1616494, "categories"=>["Biological Sciences"], "users"=>["Nora Klöting", "Nico Hesselbarth", "Martin Gericke", "Anne Kunath", "Ronald Biemann", "Rima Chakaroun", "Joanna Kosacka", "Peter Kovacs", "Matthias Kern", "Michael Stumvoll", "Bernd Fischer", "Ulrike Rolle-Kampczyk", "Ralph Feltens", "Wolfgang Otto", "Dirk K. Wissenbach", "Martin von Bergen", "Matthias Blüher"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0143190.s001", "https://dx.doi.org/10.1371/journal.pone.0143190.s002"], "stats"=>{"downloads"=>2, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Di_2_Ethylhexyl_Phthalate_DEHP_Causes_Impaired_Adipocyte_Function_and_Alters_Serum_Metabolites_/1616494", "title"=>"Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-02 03:20:42"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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