Adipose Overexpression of Heme Oxygenase-1 Does Not Protect against High Fat Diet-Induced Insulin Resistance in Mice
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{"title"=>"Adipose Overexpression of Heme Oxygenase-1 Does Not Protect against High Fat Diet-Induced Insulin Resistance in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Jun-Yuan", "last_name"=>"Huang"}, {"first_name"=>"Ming-Tsai", "last_name"=>"Chiang"}, {"first_name"=>"Lee-Young", "last_name"=>"Chau"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23390531", "doi"=>"10.1371/journal.pone.0055369", "issn"=>"1932-6203"}, "id"=>"94622900-fcc0-378d-8658-787df05ea304", "abstract"=>"Heme oxygenase-1 (HO-1) is a stress-responsive enzyme with potent anti-oxidant and anti-inflammatory activities. Previous studies have shown that systemic induction of HO-1 by chemical inducers reduces adiposity and improves insulin sensitivity. To dissect the specific function of HO-1 in adipose tissue, we generated transgenic mice with adipose HO-1 overexpression using the adipocyte-specific aP2 promoter. The transgenic (Tg) mice exhibit similar metabolic phenotype as wild type (WT) control under chow-fed condition. High fat diet (HFD) challenge significantly increased the body weights of WT and Tg mice to a similar extent. Likewise, HFD-induced glucose intolerance and insulin resistance were not much different between WT and Tg mice. Analysis of the adipose tissue gene expression revealed that the mRNA levels of adiponectin and interleukin-10 were significantly higher in chow diet-fed Tg mice as compared to WT counterparts, whereas HFD induced downregulation of adiponectin gene expression in both Tg and WT mice to a similar level. HFD-induced proinflammatory cytokine expression in adipose tissues were comparable between WT and transgenic mice. Nevertheless, immunohistochemistry and gene expression analysis showed that the number of infiltrating macrophages with preferential expression of M2 markers was significantly higher in the adipose tissue of obese Tg mice than WT mice. Further experiment demonstrated that myeloid cells from Tg mice expressed higher level of HO-1 and exhibited greater migration response toward chemoattractant in vitro. Collectively, these data indicate that HO-1 overexpression in adipocytes does not protect against HFD-induced obesity and the development of insulin resistance in mice.", "link"=>"http://www.mendeley.com/research/adipose-overexpression-heme-oxygenase1-not-protect-against-high-fat-dietinduced-insulin-resistance-m-2", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/495398"], "description"=>"<p>A, Southern blot analysis of SacI-digested mouse genomic DNA from three lines of aP2-HO-1 Tg mice. The copy numbers of each line were estimated to be 2∼5, 6∼8 and >20 copies, respectively. B, HO-1 expressions in adipose tissues from three lines of aP2-HO-1 Tg mice were examined by Western blot analysis. C, Adipose HO-1 activities in WT and HO-1 Tg mice were determined. Data shown are means ± SE. *<i>P</i><0.05 vs. WT. The number of mice in each group was four. D, HO-1 expressions in various tissues of WT and Tg mice examined by Western blot analysis. WAT, epididymal white adipose tissue; BAT, interscapular brown adipose tissue. E, HO-1 expressions in thioglycollate-induced peritoneal macrophages isolated from WT and Tg mice (n = 4/group) were examined. F, HO-1 protein levels of peritoneal macrophages were quantified by densitometry. *<i>P</i><0.05 vs the WT group.</p>", "links"=>[], "tags"=>["ap2-ho-1", "tg"], "article_id"=>165912, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_aP2_HO_1_Tg_mice_/165912", "title"=>"Generation of aP2-HO-1 Tg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:57:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/495653"], "description"=>"<p>A &B, HO-1 Tg (Tg-2 line, A; Tg-3 line, B) mice and their corresponding WT littermates were fed with a regular chow (RC) or HFD as indicated for 12 weeks. The body weights were measured every other week. The number of mice in each group was six to eight. C-F, WT and Tg mice (C&D,Tg-2 line; E&F, Tg-3 line) were fed with RC (C&E) or HFD (D&F) for 12 weeks, then the GTT and ITT assays were performed. The number of mice in each group was six to eight.</p>", "links"=>[], "tags"=>["mice", "metabolic", "phenotype", "wt"], "article_id"=>166172, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tg_mice_exhibit_similar_metabolic_phenotype_as_WT_mice_/166172", "title"=>"Tg mice exhibit similar metabolic phenotype as WT mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:59:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/495724"], "description"=>"<p>Serum samples were collected from WT and Tg mice fed with HFD for 12 weeks, and the indicated adipokine levels were then determined by ELISA kits. The numbers of mice in WT and Tg groups were six and eight, respectively.</p>", "links"=>[], "tags"=>["adipokine", "levels", "hfd-fed", "wt", "tg"], "article_id"=>166240, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_adipokine_levels_in_HFD_fed_WT_and_Tg_mice_/166240", "title"=>"Serum adipokine levels in HFD-fed WT and Tg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:59:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/495784"], "description"=>"<p>WT and Tg mice were fed with a RC diet or HFD for 12 weeks, then the animals were killed and their visceral adipose tissues were collected. A, The expressions of the indicated genes in the adipose tissues were then analyzed by quantitative PCR. The expression level of 36B4 was used as an internal control for normalization. The number of mice in each group was six to eight. <sup>#</sup><i>P</i><0.05 vs RC-fed WT group; *<i>P</i><0.05 vs the RC-fed group of the same genotype; <sup>†</sup><i>P</i><0.05 vs HFD-fed WT group. B, The levels of indicated adipokines in the WAT lysates of HFD-fed WT and Tg mice were determined by ELISA. The numbers of mice in WT and Tg groups were six and eight, respectively. *<i>P</i><0.05 vs WT group.</p>", "links"=>[], "tags"=>["wt", "tg"], "article_id"=>166306, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adipokine_gene_expression_in_WT_and_Tg_mice_/166306", "title"=>"Adipokine gene expression in WT and Tg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:00:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/495884"], "description"=>"<p>WT and Tg mice were fed with a RC or HFD for 12 weeks, and then sacrificed. A, The adipocyte size in the visceral adipose tissue sections of each group was analyzed. *<i>P</i><0.05 vs the RC-fed WT group of the same genotype. B, The adipocyte density was calculated by counting the number of adipocyte per area. *<i>P</i><0.05 vs the RC-fed group of the same genotype. C, The WAT sections were immunostained with antibody against CD31 as described in Materials and Methods. D, The normalized vascular density was quantified as the CD31-positve area divided by adipocyte density per filed. The number of animals in each group was five to six. *<i>P</i><0.05 vs the RC-fed group of the same genotype; <sup>†</sup><i>P</i><0.05 vs HFD-fed WT group.</p>", "links"=>[], "tags"=>["hfd", "adipocyte", "hypertrophy", "vascularization", "visceral", "adipose", "tissues", "wt", "tg"], "article_id"=>166395, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HFD_on_adipocyte_hypertrophy_and_vascularization_in_visceral_adipose_tissues_of_WT_and_Tg_mice_/166395", "title"=>"Effect of HFD on adipocyte hypertrophy and vascularization in visceral adipose tissues of WT and Tg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:00:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/496045"], "description"=>"<p>WT and Tg mice were fed with a RC or HFD for 12 weeks, and then sacrificed. A, The WAT sections were subjected to immunostaining using antibody against F4/80 as described in Materials and Methods. B, F4/80-positive macrophages were quantified as the percentage of adipocytes surrounded by a crown-like structure in the total adipocytes. The number of animals in each group was five to six. *<i>P</i><0.05 vs the RC-fed group of the same genotype; <sup>†</sup><i>P</i><0.05 vs HFD-fed WT group. C, The WAT sections of HFD-fed WT and Tg mice were immunostained with antibody against Mgl1 as described in Materials and Methods. D, The Mgl1 expression levels in WAT tissues of HFD-fed WT and Tg mice were examined by Western blot analysis. E, The Mgl1 protein levels were quantified by densitometry. The number of animals in each group was four. *<i>P</i><0.05 vs the WT group.</p>", "links"=>[], "tags"=>["hfd", "macrophage", "infiltration", "visceral", "adipose", "tissues", "wt", "tg"], "article_id"=>166560, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HFD_on_macrophage_infiltration_in_visceral_adipose_tissues_of_WT_and_Tg_mice_/166560", "title"=>"Effect of HFD on macrophage infiltration in visceral adipose tissues of WT and Tg mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/496162"], "description"=>"<p>Splenic CD11b<sup>+</sup> cells were isolated from WT or Tg mice. A, HO-1 expression level in each individual mouse was examined by Western blot analysis. B, HO-1 levels were quantified by densitometry (n = 3/group). *<i>P</i><0.05 vs the WT group. C, CD11b<sup>+</sup> cells isolated from each individual mouse were tested for their migration response toward 10 ng/ml of MCP-1 in the absence or presence of 10 µM SnPP. The number of mice in each group was three. *<i>P</i><0.02 vs control group of the same genotype;<sup> †</sup><i>P</i><0.02 vs WT CD11b<sup>+</sup> cells receiving MCP-1 treatment; <sup>#</sup><i>P</i><0.02 vs MCP-1-treated alone group of the same genotype.</p>", "links"=>[], "tags"=>["cells", "tg", "mice", "greater"], "article_id"=>166684, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Myeloid_cells_of_Tg_mice_exhibit_greater_migration_response_toward_MCP_1_/166684", "title"=>"Myeloid cells of Tg mice exhibit greater migration response toward MCP-1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:02:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/496347"], "description"=>"<p>The number of animals in each group is indicated in parenthesis. Eight weeks old WT or Tg mice were fed with regular chow (RC) or high fat diet (HFD). At 12 weeks on the diets, serum samples were collected, and body weight, liver and epididymal white adipose tissue (eWAT) weights were determined. Data are expressed as the mean ± SEM.</p>a<p>Significant difference between different diets within the same genotype.</p>", "links"=>[], "tags"=>["parameters", "wt", "ho-1", "tg"], "article_id"=>166871, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Genetics", "Immunology"], "users"=>["Jun-Yuan Huang", "Ming-Tsai Chiang", "Lee-Young Chau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055369.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Metabolic_parameters_of_the_WT_and_HO_1_Tg_mice_/166871", "title"=>"Metabolic parameters of the WT and HO-1 Tg mice.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 16:03:05"}

PMC Usage Stats | Further Information

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Relative Metric

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