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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2008.tde-16032009-125905
Document
Author
Full name
Daniela Tomie Furuya
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Machado, Ubiratan Fabres (President)
Nascimento, Claudia Maria da Penha Oller do
Passarelli, Marisa
Villares, Sandra Mara Ferreira
Zorn, Telma Maria Tenorio
Title in Portuguese
Efeitos da atorvastatina sobre a inflamação e resistência à insulina em camundongos obesos.
Keywords in Portuguese
Estatina
GLUT4
Inflamação
NF-kB
Obesidade
Resistência à insulina
Abstract in Portuguese
A obesidade é um estado inflamatório crônico. As estatinas têm efeito antiinflamatório e podem afetar a homeostase glicêmica. Estudos, nesse sentido são contraditórios e pouco se sabe sobre os mecanismos moleculares envolvidos. Este estudo verificou em animais obesos por glutamato monossódico (MSG) que além de apresentaram resistência à insulina in vivo, o tecido adiposo branco (TAB) desses animais mostrou aumento de infiltração de macrófagos, fosforilação de IKK-a/b, expressão de mRNA de TNF-a and IL-6, e redução de mRNA e proteína de GLUT4. O tratamento com atorvastatina por 4 semanas restabeleceu a sensibilidade à insulina in vivo, reduziu a inflamação e restabeleceu a expressão de GLUT4 no TAB dos animais obesos. Adicionalmente, esse trabalho encontrou sítios de ligação de NF-kB no promotor do gene GLUT4, sugerindo ligação entre resistência à insulina e inflamação. Em conclusão, a obesidade induzida por MSG em camundongos acompanha-se de resistência à insulina in vivo e atividade inflamatória crônica no tecido adiposo, com prejuízo da expressão de GLUT4. A atorvastatina melhorou esses aspectos, sugerindo que essa estatina tenha efeitos antiinflamatórios que podem melhorar a resistência à insulina na obesidade.
Title in English
Atorvastatin effects on inflammation and insulin resistance in obese mice.
Keywords in English
GLUT4
Inflammation
Insulin resistance
NF-kB
Obesity
Statin
Abstract in English
Obesity is a chronic inflammatory state. Statins have anti-inflammatory effects and may affect glucose homeostasis; therefore, few are known about the molecular mechanisms. Considering that inflammation contributes to insulin resistance, the aim of the present study was to investigate if atorvastatin treatment has anti-inflammatory, and consequently insulin sensitization action in white adipose tissue (WAT) of obese mice. WAT of insulin-resistant obese mice showed increased macrophage infiltration, IKK-a and IKK-b phosphorylation, TNF-a and IL-6 mRNA expression and decreased GLUT4 mRNA and protein expression. Atorvastatin restored whole-body insulin sensitivity, decreased macrophage infiltration and normalized IKK-a/b phosphorylation, TNF-a, IL-6 and GLUT4 mRNA and GLUT4 protein to control levels. Moreover, NF-kB binding sites were found in GLUT4 gene promoter, pointing out an association between insulin resistance and inflammation. Together, atorvastatin anti-inflammatory effects on WAT may be important to its local and whole-body insulin sensitization effects.
 
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Publishing Date
2009-03-23
 
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