Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2008 |
| Outros Autores: | , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/32324 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. |
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Maya-Monteiro, Clarissa M.Almeida, Patricia E.D'Avila, HeloisaMartins, Aline S.Rezende, Ana PaulaFaria Neto, Hugo C. CastroBozza, Patrícia T.2019-04-02T12:47:06Z2019-04-02T12:47:06Z2008MAYA-MONTEIRO, Clarissa M. et al. Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism. The Journal of Biological Chemistry, v. 283, n. 4, p. 2203-2210, Jan. 2008.0021-9258https://www.arca.fiocruz.br/handle/icict/3232410.1074/jbc.M7067062001083-351XengAmerican Society for Biochemistry and Molecular BiologyLeptinaFormação Corporal Lipídica de MacrófagosFosfatidilinositol 3-QuinaseMamíferosRapamicinaLeptinMacrophage Lipid Body FormationMammaliansPhosphatidylinositol 3-KinaseRapamycinLeptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanisminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Lipid bodies (lipid droplets) are emerging as dynamic organelles with roles in lipid metabolism and inflammation. Here we investigated the roles of leptin in signaling pathways involved in cytoplasmic lipid body biogenesis and leukotriene B(4) synthesis in macrophages. Our results demonstrated that leptin directly activated macrophages and induced the formation of adipose differentiation-related protein-enriched lipid bodies. Newly formed lipid bodies were sites of 5-lipoxygenase localization and correlated with an enhanced capacity of leukotriene B(4) production. We demonstrated that leptin-induced macrophage activation was dependent on phosphatidylinositol 3-kinase (PI3K) activity, since the lipid body formation was inhibited by LY294002 and was absent in the PI3K knock-out mice. Leptin induces phosphorylation of p70(S6K) and 4EBP1 key downstream signaling intermediates of the mammalian target of rapamycin (mTOR) pathway in a rapamycin-sensitive mechanism. The mTOR inhibitor, rapamycin, inhibited leptin-induced lipid body formation, both in vivo and in vitro. In addition, rapamycin inhibited leptin-induced adipose differentiation-related protein accumulation in macrophages and lipid body-dependent leukotriene synthesis, demonstrating a key role for mTOR in lipid body biogenesis and function. Our results establish PI3K/mTOR as an important signaling pathway for leptin-induced cytoplasmic lipid body biogenesis and adipose differentiation-related protein accumulation. Furthermore, we demonstrate a previously unrecognized link between intracellular (mTOR) and systemic (leptin) nutrient sensors in macrophage lipid metabolism. Leptin-induced increased formation of cytoplasmic lipid bodies and enhanced inflammatory mediator production in macrophages may have implications for obesity-related cardiovascular diseases.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/32324/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALClarissaM_Monteiro_etal_IOC_2008.pdfClarissaM_Monteiro_etal_IOC_2008.pdfapplication/pdf346629https://www.arca.fiocruz.br/bitstream/icict/32324/2/ClarissaM_Monteiro_etal_IOC_2008.pdfc62cd752a16b4f0d0c0c345abe8feba2MD52TEXTClarissaM_Monteiro_etal_IOC_2008.pdf.txtClarissaM_Monteiro_etal_IOC_2008.pdf.txtExtracted texttext/plain48976https://www.arca.fiocruz.br/bitstream/icict/32324/3/ClarissaM_Monteiro_etal_IOC_2008.pdf.txta44e2912a02077251bee68bf08a59f70MD53icict/323242023-09-05 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| dc.title.pt_BR.fl_str_mv |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| title |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| spellingShingle |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism Maya-Monteiro, Clarissa M. Leptina Formação Corporal Lipídica de Macrófagos Fosfatidilinositol 3-Quinase Mamíferos Rapamicina Leptin Macrophage Lipid Body Formation Mammalians Phosphatidylinositol 3-Kinase Rapamycin |
| title_short |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| title_full |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| title_fullStr |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| title_full_unstemmed |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| title_sort |
Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism |
| author |
Maya-Monteiro, Clarissa M. |
| author_facet |
Maya-Monteiro, Clarissa M. Almeida, Patricia E. D'Avila, Heloisa Martins, Aline S. Rezende, Ana Paula Faria Neto, Hugo C. Castro Bozza, Patrícia T. |
| author_role |
author |
| author2 |
Almeida, Patricia E. D'Avila, Heloisa Martins, Aline S. Rezende, Ana Paula Faria Neto, Hugo C. Castro Bozza, Patrícia T. |
| author2_role |
author author author author author author |
| dc.contributor.author.fl_str_mv |
Maya-Monteiro, Clarissa M. Almeida, Patricia E. D'Avila, Heloisa Martins, Aline S. Rezende, Ana Paula Faria Neto, Hugo C. Castro Bozza, Patrícia T. |
| dc.subject.other.pt_BR.fl_str_mv |
Leptina Formação Corporal Lipídica de Macrófagos Fosfatidilinositol 3-Quinase Mamíferos Rapamicina |
| topic |
Leptina Formação Corporal Lipídica de Macrófagos Fosfatidilinositol 3-Quinase Mamíferos Rapamicina Leptin Macrophage Lipid Body Formation Mammalians Phosphatidylinositol 3-Kinase Rapamycin |
| dc.subject.en.pt_BR.fl_str_mv |
Leptin Macrophage Lipid Body Formation Mammalians Phosphatidylinositol 3-Kinase Rapamycin |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. |
| publishDate |
2008 |
| dc.date.issued.fl_str_mv |
2008 |
| dc.date.accessioned.fl_str_mv |
2019-04-02T12:47:06Z |
| dc.date.available.fl_str_mv |
2019-04-02T12:47:06Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.citation.fl_str_mv |
MAYA-MONTEIRO, Clarissa M. et al. Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism. The Journal of Biological Chemistry, v. 283, n. 4, p. 2203-2210, Jan. 2008. |
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https://www.arca.fiocruz.br/handle/icict/32324 |
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0021-9258 |
| dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M706706200 |
| dc.identifier.eissn.none.fl_str_mv |
1083-351X |
| identifier_str_mv |
MAYA-MONTEIRO, Clarissa M. et al. Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism. The Journal of Biological Chemistry, v. 283, n. 4, p. 2203-2210, Jan. 2008. 0021-9258 10.1074/jbc.M706706200 1083-351X |
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eng |
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American Society for Biochemistry and Molecular Biology |
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American Society for Biochemistry and Molecular Biology |
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