Effects of tumor necrosis factor alpha on leptin secretion and gene expression : relationship to changes of glucose metabolism in isolated rat adipocytes
Our objective was to determine the effects of prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) on leptin secretion from and leptin (OB) gene expression in isolated adipocytes. Because glucose uptake and the metabolism of glucose beyond lactate are important determinants of leptin produc...
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| Veröffentlicht in: | International Journal of Obesity 1999-08, Vol.23 (8), p.896-903 |
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| container_title | International Journal of Obesity |
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| creator | MEDINA, E. A STANHOPE, K. L MIZUNO, T. M MOBBS, C. V GREGOIRE, F HUBBARD, N. E ERICKSON, K. L HAVEL, P. J |
| description | Our objective was to determine the effects of prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) on leptin secretion from and leptin (OB) gene expression in isolated adipocytes. Because glucose uptake and the metabolism of glucose beyond lactate are important determinants of leptin production in adipocytes, we examined the effects of TNF-alpha on glucose uptake and lactate production and their relationship to leptin secretion.
Isolated rat adipocytes were anchored in a defined matrix of basement membrane components and cultured with media containing 5 mM glucose, 0.16 nM insulin and several concentrations of TNF-alpha. Leptin secretion, steady-state levels of leptin mRNA levels, glucose uptake, and lactate production were assessed over 96 h.
TNF-alpha at concentrations of 0.024, 0.24, 2.4 and 24 ng/ml did not affect leptin secretion over 24 h. TNF-alpha at concentrations of 0.24 to 24 ng/ml significantly inhibited leptin secretion over 96 h by 19-60%. TNF-alpha at concentrations of 0.024 to 24 ng/ml significantly decreased steady-state levels of leptin mRNA after 96 h by 32-95%. In addition, TNF-alpha at concentrations of 2.4 and 24 ng/ml significantly increased glucose uptake and lactate production over 96 h by 30-57%. TNF-alpha at a concentration of 0.024 ng/ml did not affect leptin secretion, glucose uptake or lactate production. Overall, for the TNF-alpha concentrations tested, leptin secretion was inversely related to the percent of glucose carbon released as lactate; however, TNF-alpha did not induce a proportional increase of lactate production from glucose.
Short-term (24 h) exposure of isolated adipocytes to TNF-alpha does not affect leptin secretion. Prolonged exposure to TNF-alpha produces a concentration-dependent inhibition of leptin secretion and gene expression. This suggests that the acute effect of TNF-alpha to increase circulating leptin levels in vivo may be indirect. TNF-alpha at higher concentrations increases glucose uptake, but does not increase the conversion of glucose to lactate. Therefore, TNF-alpha appears to induce a dissociation between adipocyte glucose metabolism and leptin production. |
| doi_str_mv | 10.1038/sj.ijo.0800970 |
| format | Article |
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Isolated rat adipocytes were anchored in a defined matrix of basement membrane components and cultured with media containing 5 mM glucose, 0.16 nM insulin and several concentrations of TNF-alpha. Leptin secretion, steady-state levels of leptin mRNA levels, glucose uptake, and lactate production were assessed over 96 h.
TNF-alpha at concentrations of 0.024, 0.24, 2.4 and 24 ng/ml did not affect leptin secretion over 24 h. TNF-alpha at concentrations of 0.24 to 24 ng/ml significantly inhibited leptin secretion over 96 h by 19-60%. TNF-alpha at concentrations of 0.024 to 24 ng/ml significantly decreased steady-state levels of leptin mRNA after 96 h by 32-95%. In addition, TNF-alpha at concentrations of 2.4 and 24 ng/ml significantly increased glucose uptake and lactate production over 96 h by 30-57%. TNF-alpha at a concentration of 0.024 ng/ml did not affect leptin secretion, glucose uptake or lactate production. Overall, for the TNF-alpha concentrations tested, leptin secretion was inversely related to the percent of glucose carbon released as lactate; however, TNF-alpha did not induce a proportional increase of lactate production from glucose.
Short-term (24 h) exposure of isolated adipocytes to TNF-alpha does not affect leptin secretion. Prolonged exposure to TNF-alpha produces a concentration-dependent inhibition of leptin secretion and gene expression. This suggests that the acute effect of TNF-alpha to increase circulating leptin levels in vivo may be indirect. TNF-alpha at higher concentrations increases glucose uptake, but does not increase the conversion of glucose to lactate. Therefore, TNF-alpha appears to induce a dissociation between adipocyte glucose metabolism and leptin production.</description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/sj.ijo.0800970</identifier><identifier>PMID: 10490793</identifier><identifier>CODEN: IJOBDP</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Adipocytes - metabolism ; Animals ; Biological and medical sciences ; Blotting, Northern ; Cells, Cultured ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions ; Glucose - metabolism ; Insulin - metabolism ; Lactic Acid - metabolism ; Leptin ; Male ; Proteins - genetics ; Proteins - metabolism ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - analysis ; Time Factors ; Tumor Necrosis Factor-alpha - metabolism ; Vertebrates: endocrinology</subject><ispartof>International Journal of Obesity, 1999-08, Vol.23 (8), p.896-903</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-ef31f4da101742608cb167d09d6b8cb2043b001818f553a659709f455b54faf3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1914911$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10490793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MEDINA, E. A</creatorcontrib><creatorcontrib>STANHOPE, K. L</creatorcontrib><creatorcontrib>MIZUNO, T. M</creatorcontrib><creatorcontrib>MOBBS, C. V</creatorcontrib><creatorcontrib>GREGOIRE, F</creatorcontrib><creatorcontrib>HUBBARD, N. E</creatorcontrib><creatorcontrib>ERICKSON, K. L</creatorcontrib><creatorcontrib>HAVEL, P. J</creatorcontrib><title>Effects of tumor necrosis factor alpha on leptin secretion and gene expression : relationship to changes of glucose metabolism in isolated rat adipocytes</title><title>International Journal of Obesity</title><addtitle>Int J Obes Relat Metab Disord</addtitle><description>Our objective was to determine the effects of prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) on leptin secretion from and leptin (OB) gene expression in isolated adipocytes. Because glucose uptake and the metabolism of glucose beyond lactate are important determinants of leptin production in adipocytes, we examined the effects of TNF-alpha on glucose uptake and lactate production and their relationship to leptin secretion.
Isolated rat adipocytes were anchored in a defined matrix of basement membrane components and cultured with media containing 5 mM glucose, 0.16 nM insulin and several concentrations of TNF-alpha. Leptin secretion, steady-state levels of leptin mRNA levels, glucose uptake, and lactate production were assessed over 96 h.
TNF-alpha at concentrations of 0.024, 0.24, 2.4 and 24 ng/ml did not affect leptin secretion over 24 h. TNF-alpha at concentrations of 0.24 to 24 ng/ml significantly inhibited leptin secretion over 96 h by 19-60%. TNF-alpha at concentrations of 0.024 to 24 ng/ml significantly decreased steady-state levels of leptin mRNA after 96 h by 32-95%. In addition, TNF-alpha at concentrations of 2.4 and 24 ng/ml significantly increased glucose uptake and lactate production over 96 h by 30-57%. TNF-alpha at a concentration of 0.024 ng/ml did not affect leptin secretion, glucose uptake or lactate production. Overall, for the TNF-alpha concentrations tested, leptin secretion was inversely related to the percent of glucose carbon released as lactate; however, TNF-alpha did not induce a proportional increase of lactate production from glucose.
Short-term (24 h) exposure of isolated adipocytes to TNF-alpha does not affect leptin secretion. Prolonged exposure to TNF-alpha produces a concentration-dependent inhibition of leptin secretion and gene expression. This suggests that the acute effect of TNF-alpha to increase circulating leptin levels in vivo may be indirect. TNF-alpha at higher concentrations increases glucose uptake, but does not increase the conversion of glucose to lactate. Therefore, TNF-alpha appears to induce a dissociation between adipocyte glucose metabolism and leptin production.</description><subject>Adipocytes - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Cells, Cultured</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions</subject><subject>Glucose - metabolism</subject><subject>Insulin - metabolism</subject><subject>Lactic Acid - metabolism</subject><subject>Leptin</subject><subject>Male</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - analysis</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Vertebrates: endocrinology</subject><issn>0307-0565</issn><issn>1476-5497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkD1v2zAQhomiReOkXTsWHLrKPZqkJHYLAqcpEKBLdoGijjYNSRR4NND8lPzb0LGBdLqv973DPYx9E7AWINufdFiHQ1xDC2Aa-MBWQjV1pZVpPrIVSGgq0LW-YtdEBwDQGjaf2ZUAZaAxcsVett6jy8Sj5_k4xcRndClSIO6ty6W247K3PM58xCWHmVOZYw6lYeeB73BGjv-WhESn3i-ecLSnMe3DwnPkbm_nHb4d2I1HFwn5hNn2cQw08bIwUCwOHHiymdshLNE9Z6Qv7JO3I-HXS7xhT_fbp7uH6vHv7z93t4-Vk0bnCr0UXg1WgGjUpobW9aJuBjBD3Zd8A0r2AKIVrdda2loXTMYrrXutvPXyhq3Pa09fU0LfLSlMNj13AroT4o4OXUHcXRAXw_ezYTn2Ew7_yc9Mi-DHRWDJ2dEnO7tA7zojlBFCvgKhLIgf</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>MEDINA, E. A</creator><creator>STANHOPE, K. L</creator><creator>MIZUNO, T. M</creator><creator>MOBBS, C. V</creator><creator>GREGOIRE, F</creator><creator>HUBBARD, N. E</creator><creator>ERICKSON, K. L</creator><creator>HAVEL, P. J</creator><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>19990801</creationdate><title>Effects of tumor necrosis factor alpha on leptin secretion and gene expression : relationship to changes of glucose metabolism in isolated rat adipocytes</title><author>MEDINA, E. A ; STANHOPE, K. L ; MIZUNO, T. M ; MOBBS, C. V ; GREGOIRE, F ; HUBBARD, N. E ; ERICKSON, K. L ; HAVEL, P. 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Adaptive reactions</topic><topic>Glucose - metabolism</topic><topic>Insulin - metabolism</topic><topic>Lactic Acid - metabolism</topic><topic>Leptin</topic><topic>Male</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - analysis</topic><topic>Time Factors</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MEDINA, E. A</creatorcontrib><creatorcontrib>STANHOPE, K. L</creatorcontrib><creatorcontrib>MIZUNO, T. M</creatorcontrib><creatorcontrib>MOBBS, C. V</creatorcontrib><creatorcontrib>GREGOIRE, F</creatorcontrib><creatorcontrib>HUBBARD, N. E</creatorcontrib><creatorcontrib>ERICKSON, K. L</creatorcontrib><creatorcontrib>HAVEL, P. 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J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of tumor necrosis factor alpha on leptin secretion and gene expression : relationship to changes of glucose metabolism in isolated rat adipocytes</atitle><jtitle>International Journal of Obesity</jtitle><addtitle>Int J Obes Relat Metab Disord</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>23</volume><issue>8</issue><spage>896</spage><epage>903</epage><pages>896-903</pages><issn>0307-0565</issn><eissn>1476-5497</eissn><coden>IJOBDP</coden><abstract>Our objective was to determine the effects of prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) on leptin secretion from and leptin (OB) gene expression in isolated adipocytes. Because glucose uptake and the metabolism of glucose beyond lactate are important determinants of leptin production in adipocytes, we examined the effects of TNF-alpha on glucose uptake and lactate production and their relationship to leptin secretion.
Isolated rat adipocytes were anchored in a defined matrix of basement membrane components and cultured with media containing 5 mM glucose, 0.16 nM insulin and several concentrations of TNF-alpha. Leptin secretion, steady-state levels of leptin mRNA levels, glucose uptake, and lactate production were assessed over 96 h.
TNF-alpha at concentrations of 0.024, 0.24, 2.4 and 24 ng/ml did not affect leptin secretion over 24 h. TNF-alpha at concentrations of 0.24 to 24 ng/ml significantly inhibited leptin secretion over 96 h by 19-60%. TNF-alpha at concentrations of 0.024 to 24 ng/ml significantly decreased steady-state levels of leptin mRNA after 96 h by 32-95%. In addition, TNF-alpha at concentrations of 2.4 and 24 ng/ml significantly increased glucose uptake and lactate production over 96 h by 30-57%. TNF-alpha at a concentration of 0.024 ng/ml did not affect leptin secretion, glucose uptake or lactate production. Overall, for the TNF-alpha concentrations tested, leptin secretion was inversely related to the percent of glucose carbon released as lactate; however, TNF-alpha did not induce a proportional increase of lactate production from glucose.
Short-term (24 h) exposure of isolated adipocytes to TNF-alpha does not affect leptin secretion. Prolonged exposure to TNF-alpha produces a concentration-dependent inhibition of leptin secretion and gene expression. This suggests that the acute effect of TNF-alpha to increase circulating leptin levels in vivo may be indirect. TNF-alpha at higher concentrations increases glucose uptake, but does not increase the conversion of glucose to lactate. Therefore, TNF-alpha appears to induce a dissociation between adipocyte glucose metabolism and leptin production.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>10490793</pmid><doi>10.1038/sj.ijo.0800970</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | International Journal of Obesity, 1999-08, Vol.23 (8), p.896-903 |
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| subjects | Adipocytes - metabolism Animals Biological and medical sciences Blotting, Northern Cells, Cultured Fundamental and applied biological sciences. Psychology Gene Expression General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions Glucose - metabolism Insulin - metabolism Lactic Acid - metabolism Leptin Male Proteins - genetics Proteins - metabolism Rats Rats, Sprague-Dawley RNA, Messenger - analysis Time Factors Tumor Necrosis Factor-alpha - metabolism Vertebrates: endocrinology |
| title | Effects of tumor necrosis factor alpha on leptin secretion and gene expression : relationship to changes of glucose metabolism in isolated rat adipocytes |
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