Salsalate and Adiponectin Improve Palmitate-Induced Insulin Resistance via Inhibition of Selenoprotein P through the AMPK-FOXO1α Pathway
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{"title"=>"Salsalate and Adiponectin Improve Palmitate-Induced Insulin Resistance via Inhibition of Selenoprotein P through the AMPK-FOXO1α Pathway", "type"=>"journal", "authors"=>[{"first_name"=>"Tae Woo", "last_name"=>"Jung", "scopus_author_id"=>"10139325600"}, {"first_name"=>"Hae Yoon", "last_name"=>"Choi", "scopus_author_id"=>"37058564900"}, {"first_name"=>"So Young", "last_name"=>"Lee", "scopus_author_id"=>"55871679600"}, {"first_name"=>"Ho Cheol", "last_name"=>"Hong", "scopus_author_id"=>"51763862000"}, {"first_name"=>"Sae Jeong", "last_name"=>"Yang", "scopus_author_id"=>"36011294300"}, {"first_name"=>"Hye Jin", "last_name"=>"Yoo", "scopus_author_id"=>"36442032000"}, {"first_name"=>"Byung Soo", "last_name"=>"Youn", "scopus_author_id"=>"7005009217"}, {"first_name"=>"Sei Hyun", "last_name"=>"Baik", "scopus_author_id"=>"7102833918"}, {"first_name"=>"Kyung Mook", "last_name"=>"Choi", "scopus_author_id"=>"7403949874"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23825542", "scopus"=>"2-s2.0-84879161441", "doi"=>"10.1371/journal.pone.0066529", "issn"=>"19326203", "sgr"=>"84879161441", "pui"=>"369142417", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"162a43a5-72fb-3347-bb1c-dd422fca39f7", "abstract"=>"Selenoprotein P (SeP) was recently identified as a hepatokine that induces insulin resistance (IR) in rodents and humans. Recent clinical trials have shown that salsalate, a prodrug of salicylate, significantly lowers blood glucose levels and increases adiponectin concentrations. We examined the effects of salsalate and full length-adiponectin (fAd) on the expression of SeP under hyperlipidemic conditions and explored their regulatory mechanism on SeP. In palmitate-treated HepG2 cells as well as high fat diet (HFD)-fed male Spraque Dawley (SD) rats and male db/db mice, SeP expression and its regulatory pathway, including AMPK-FOXO1α, were evaluated after administration of salsalate and salicylate. Palmitate treatment significantly increased SeP expression and aggravated IR, while knock-down of SeP by siRNA restored these changes in HepG2 cells. Palmitate-induced SeP expression was inhibited by both salsalate and salicylate, which was mediated by AMPK activation, and was blocked by AMPK siRNA or an inhibitor of AMPK. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift (EMSA) assay showed that salsalate suppressed SeP expression by AMPK-mediated phosphorylation of FOXO1α. Moreover, fAd also reduced palmitate-induced SeP expression through the activation of AMPK, which results in improved IR. Both salsalate and salicylate treatment significantly improved glucose intolerance and insulin sensitivity, accompanied by reduced SeP mRNA and protein expression in HFD-fed rats and db/db mice, respectively. Taken together, we found that salsalate and adiponectin ameliorated palmitate-induced IR in hepatocytes via SeP inhibition through the AMPK-FOXO1α pathway. The regulation of SeP might be a novel mechanism mediating the anti-diabetic effects of salsalate and adiponectin.", "link"=>"http://www.mendeley.com/research/salsalate-adiponectin-improve-palmitateinduced-insulin-resistance-via-inhibition-selenoprotein-p-thr", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>6, "Sports and Recreations"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Japan"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1092388"], "description"=>"<p>(A) HepG2 cells were incubated with different concentrations of salsalate for 24 hr or salsalate (10 mM) for different time periods. 20 µM compound C (C), AMPK siRNA (siA), and 2 mM AICAR (A) were tested. (B) Control (scramble siRNA) or AMPK siRNA (siA)-transfected HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salsalate (S) for 24 hr, and SeP expression was determined by Western blot analysis. (C) Control or 20 µM compound C (C)-treated HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salsalate (S) for 24 hr, and SeP expression was determined by Western blot analysis. (D) Control or AICAR (A)-treated HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salsalate (S) for 24 hr, and SeP expression was determined by Western blot analysis. β-actin was used as an internal standard. Means ± SEMs were calculated from the results of three independent experiments.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "involves", "inhibitory", "salsalate", "palmitate-induced", "selenoprotein", "hepg2"], "article_id"=>724608, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g003", "stats"=>{"downloads"=>2, "page_views"=>147, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AMPK_involves_in_the_inhibitory_effect_of_salsalate_on_palmitate_induced_selenoprotein_P_in_HepG2_cells_/724608", "title"=>"AMPK involves in the inhibitory effect of salsalate on palmitate-induced selenoprotein P in HepG2 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:16:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092404"], "description"=>"<p>Schematic diagram illustrating the mechanism underlying the effect of salsalate and adiponectin on palmitate-induced insulin resistance.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "diagram", "illustrating", "salsalate", "adiponectin", "palmitate-induced", "insulin"], "article_id"=>724621, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g007", "stats"=>{"downloads"=>3, "page_views"=>219, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_diagram_illustrating_the_mechanism_underlying_the_effect_of_salsalate_and_adiponectin_on_palmitate_induced_insulin_resistance_/724621", "title"=>"Schematic diagram illustrating the mechanism underlying the effect of salsalate and adiponectin on palmitate-induced insulin resistance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:17:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092381"], "description"=>"<p>Control (scramble siRNA) or SeP siRNA-transfected HepG2 cells were incubated with 250 µM palmitate for 24 hr. The phosphorylation of IRS-1 (Tyr) and Akt (Ser) was determined by Western blot analysis. Insulin (10 nM) was used to stimulate IRS-1 and Akt for 3 min. Means ± SEMs were calculated from the results of three independent experiments.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "impairs", "insulin", "selenoprotein", "knock-down", "restores", "hepg2"], "article_id"=>724602, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g001", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Palmitate_significantly_impairs_insulin_signaling_and_selenoprotein_P_knock_down_restores_these_changes_in_HepG2_cells_/724602", "title"=>"Palmitate significantly impairs insulin signaling, and selenoprotein P knock-down restores these changes in HepG2 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:16:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092398"], "description"=>"<p>(A) SeP protein expression was determined by Western blot analysis, (B) SeP mRNA expression was determined by real-time PCR analysis in normal fat diet (NFD), HFD, and HFD plus salsalate (HFD+Sal) treated SD rats (n = 7 animals per treatment group). (C) SeP protein expression was determined by Western blot analysis, (D) SeP mRNA expression was determined by real-time PCR analysis in B6 mice (Lean), <i>db/db</i> mice (db), and <i>db/db</i> mice plus salicylate (db+Sac) (n = 7 animals per treatment group). (E) Intra-peritoneal glucose tolerance test (IPGTT), (F) Insulin tolerance test (ITT) in normal fat diet (NFD,•), HFD (○), and HFD plus salsalate (HFD+Sal, ▾) treated SD rats (n = 7 animals per treatment group). (G) Intra-peritoneal glucose tolerance test (IPGTT), (H) Insulin tolerance test (ITT) in B6 mice (Lean, •), <i>db/db</i> mice (db, ○), and <i>db/db</i> mice plus salicylate (db+Sac, ▾) (n = 7 animals per treatment group). Means ± SEMs were calculated from the data for seven separate animals.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "salsalate", "salicylate", "treatments", "diet-", "spontaneously-induced", "insulin", "hepatic", "selenoprotein"], "article_id"=>724615, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g006", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systemic_salsalate_or_salicylate_treatments_prevent_high_fat_diet_or_spontaneously_induced_insulin_resistance_as_well_as_hepatic_selenoprotein_P_expression_/724615", "title"=>"Systemic salsalate or salicylate treatments prevent high fat diet- or spontaneously-induced insulin resistance as well as hepatic selenoprotein P expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:16:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092384"], "description"=>"<p>(A) HepG2 cells were incubated with 250 µM palmitate (P) and different concentrations (mM) of salsalate for 24 hrs. After incubation, cell extracts were harvested and subjected to Western blot analysis to determine SeP expression. β-actin was used as an internal standard. (B) HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salsalate (S) for different periods (hr). After incubation, cell extracts were harvested and subjected to Western blot analysis to determine SeP levels. β-actin was used as an internal standard. Means ± SEMs were calculated from the results of three independent experiments.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "inhibits", "palmitate-induced", "selenoprotein", "dose-", "time-dependent", "manners", "hepg2"], "article_id"=>724605, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g002", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Salsalate_inhibits_palmitate_induced_selenoprotein_P_expression_in_both_dose_and_time_dependent_manners_in_HepG2_cells_/724605", "title"=>"Salsalate inhibits palmitate-induced selenoprotein P expression in both dose- and time-dependent manners in HepG2 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:16:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092396"], "description"=>"<p>(A and B) HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salsalate (S) or without salsalate for 24 hrs. (C) HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salicylate (Sa) or without salicylate for 24 hrs. IRS-1 and Akt phosphorylation was measured by Western blot analysis. (D and E) HepG2 cells were incubated with different concentrations of fAd for 24 hr or fAd (30 µg/ml) for different time periods. HepG2 cells were incubated with 250 µM palmitate (P) and fAd (Ad) or without fAd for 24 hrs. AMPK, IRS-1, and Akt phosphorylations and SeP expression were determined by Western blot analysis. Insulin (10 nM) was used to stimulate IRS-1 and Akt for 3 min. Means ± SEMs were calculated from the results of three independent experiments.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "full-length", "adiponectin", "attenuate", "palmitate-induced", "insulin", "hepg2"], "article_id"=>724613, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g005", "stats"=>{"downloads"=>2, "page_views"=>69, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Salsalate_salicylate_and_full_length_adiponectin_attenuate_palmitate_induced_insulin_resistance_in_HepG2_cells_/724613", "title"=>"Salsalate, salicylate, and full-length adiponectin attenuate palmitate-induced insulin resistance in HepG2 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:16:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092392"], "description"=>"<p>(A) HepG2 cells were incubated with 250 µM palmitate (P) and 10 mM salsalate (S) or without salsalate or 20 µM compound C (C) for 24 hrs. FOXO1α phosphorylation (Ser) was determined by Western blot analysis with anti-FOXO1α and anti-phospho FOXO1α. (B) FOXO1α binding to the SeP promoter was determined using a ChIP assay. (C) Nuclear extracts from the above mentioned incubated cells were subjected to EMSA. For the supershift assay, an anti-FOXO1α antibody was used. An unlabeled probe was used to assess the specific binding of FOXO1α to the SeP promoter. Means ± SEMs were calculated from the results of three independent experiments.</p>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "inhibitory", "salsalate", "palmitate-induced", "selenoprotein", "ampk-dependent"], "article_id"=>724609, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066529.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_inhibitory_effect_of_salsalate_on_palmitate_induced_selenoprotein_P_is_involved_in_the_AMPK_dependent_FOXO1_945_pathway_/724609", "title"=>"The inhibitory effect of salsalate on palmitate-induced selenoprotein P is involved in the AMPK-dependent FOXO1α pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:16:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1092409", "https://ndownloader.figshare.com/files/1092410", "https://ndownloader.figshare.com/files/1092412"], "description"=>"<div><p>Selenoprotein P (SeP) was recently identified as a hepatokine that induces insulin resistance (IR) in rodents and humans. Recent clinical trials have shown that salsalate, a prodrug of salicylate, significantly lowers blood glucose levels and increases adiponectin concentrations. We examined the effects of salsalate and full length-adiponectin (fAd) on the expression of SeP under hyperlipidemic conditions and explored their regulatory mechanism on SeP. In palmitate-treated HepG2 cells as well as high fat diet (HFD)-fed male Spraque Dawley (SD) rats and male <i>db/db</i> mice, SeP expression and its regulatory pathway, including AMPK-FOXO1α, were evaluated after administration of salsalate and salicylate. Palmitate treatment significantly increased SeP expression and aggravated IR, while knock-down of SeP by siRNA restored these changes in HepG2 cells. Palmitate-induced SeP expression was inhibited by both salsalate and salicylate, which was mediated by AMPK activation, and was blocked by AMPK siRNA or an inhibitor of AMPK. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift (EMSA) assay showed that salsalate suppressed SeP expression by AMPK-mediated phosphorylation of FOXO1α. Moreover, fAd also reduced palmitate-induced SeP expression through the activation of AMPK, which results in improved IR. Both salsalate and salicylate treatment significantly improved glucose intolerance and insulin sensitivity, accompanied by reduced SeP mRNA and protein expression in HFD-fed rats and <i>db/db</i> mice, respectively. Taken together, we found that salsalate and adiponectin ameliorated palmitate-induced IR in hepatocytes via SeP inhibition through the AMPK-FOXO1α pathway. The regulation of SeP might be a novel mechanism mediating the anti-diabetic effects of salsalate and adiponectin.</p></div>", "links"=>[], "tags"=>["Biochemistry", "Model organisms", "Animal models", "mouse", "rat", "Molecular cell biology", "medicinal chemistry", "Endocrinology", "Gastroenterology and hepatology", "Non-clinical medicine", "nutrition", "obesity", "adiponectin", "palmitate-induced", "insulin", "inhibition", "selenoprotein"], "article_id"=>724626, "categories"=>["Medicine", "Chemistry", "Biological Sciences"], "users"=>["Tae Woo Jung", "Hae Yoon Choi", "So Young Lee", "Ho Cheol Hong", "Sae Jeong Yang", "Hye Jin Yoo", "Byung-Soo Youn", "Sei Hyun Baik", "Kyung Mook Choi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066529.s001", "https://dx.doi.org/10.1371/journal.pone.0066529.s002", "https://dx.doi.org/10.1371/journal.pone.0066529.s003"], "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Salsalate_and_Adiponectin_Improve_Palmitate_Induced_Insulin_Resistance_via_Inhibition_of_Selenoprotein_P_through_the_AMPK_FOXO1_945_Pathway_/724626", "title"=>"Salsalate and Adiponectin Improve Palmitate-Induced Insulin Resistance via Inhibition of Selenoprotein P through the AMPK-FOXO1α Pathway", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-18 01:17:06"}

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Relative Metric

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