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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2015.tde-08122015-185802
Document
Author
Full name
Helena Angelica Pereira Batatinha
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Rosa Neto, José Cesar (President)
Brum, Patricia Chakur
Ortis, Fernanda
Title in Portuguese
Exercício aeróbio crônico reduz o acúmulo de gordura hepático, mas promove inflamação no fígado de camundongos PPAR-alpha knockout, via inibição do PPAR-gama.
Keywords in Portuguese
Inflamação
NAFLD
Obesidade
PPARα
PPARγ
Resistência à insulina
Treinamento aeróbio crônico
Abstract in Portuguese
A NAFLD é uma das principais patologias de fígado. Estudos reportam o exercício físico como um dos principais alvos terapêuticos para esta doença. Verificamos se o treinamento melhora a resistência à insulina, inflamação e esteatose hepática causados pela dieta hiperlipídica (HF) e se o PPAR-alpha está envolvido neste processo. Animais selvagens C57BL6 (WT) e knockout para PPARα (KO) foram alimentados com dieta padrão ou HF durante 12 semanas e treinados por 8 semana. Metade dos animais KO treinados receberam rosiglitazona. A dieta HF aumentou TAG hepático, e resistência periférica à insulina levando a NALFD. O treinamento foi eficiente em reduzir esses parâmetros em ambos genótipos. O desenvolvimento da NAFLD não foi associado à inflamação hepática, entretanto animais KO treinados apresentaram uma resposta inflamatória exacerbada, causada pela redução de PPARγ. Quando eles receberam rosi apresentaram melhora no quadro inflamatório hepático e na resistência à insulina. O exercício diminuiu os danos causados pela dieta HF independente do PPARα; a ausência do PPARα junto com exercício leva a queda na expressão de PPARγ, e a uma resposta inflamatória exacerbada, que é revertida pela administração da rosiglitazona.
Title in English
Aerobic Exercise decreases NAFLD, but promotes liver inflammation in PPAR-alpha knockout mice via PPAR-gamma inhibition.
Keywords in English
Chronic aerobic exercise
Inflammation
Insulin resistance
NAFLD
Obesity
PPARα
PPARγ
Abstract in English
NAFLD is one of the main liver diseases. Studies have shown the beneficial effects of exercise on reverse NAFLD. We verify whether exercise improve insulin resistance, liver inflammation and steatohepatitis caused by a high fat diet (HF) and whether PPARα is involved in these actions. C57BL6 wild type (WT) and PPAR-α knockout (KO) mice were fed with a standard (SD) or HF during 12 weeks and trained on a treadmill during 8 weeks, half of KO trained animals received 15mg/kg/day of rosiglitazone. HF diet increased TAG in the liver and peripheral insulin resistance leading to NAFLD. Exercise reduced all this parameters in both animals genotype. NAFLD was not associated with inflammation, however KO mice when trained presented an inflammatory response that was caused by a decrease on PPARγ. When these mice were treated with rosiglitazone, they presented decrease on inflammatory cytokines as well as improvement on insulin sensitivity. Exercise improved the damage caused by a HF independently of PPARα and the absence of PPARα together with exercise leads to decrease on PPARγ expression and an inflammatory response, which was attenuated by rosiglitazone administration.
 
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Publishing Date
2015-12-08
 
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