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Master's Dissertation
DOI
10.11606/D.42.2010.tde-19052010-130712
Document
Author
Full name
Beatriz de Souza Amorim
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Ferreira, Cecilia Helena de Azevedo Gouveia (President)
Christoffolete, Marcelo Augusto
Ribeiro, Miriam Oliveira
Title in Portuguese
Papel do TR na termogênese induzida pela dieta.
Keywords in Portuguese
Análogos do TRB
Hormônios tiroidianos
Metabolismo energético
Obesidade
Receptores hormonais
Termogênese
Abstract in Portuguese
O hormônio tireoideano (T3) desempenha papel importante no desenvolvimento, no crescimento e no metabolismo celular. Um dos seus principais efeitos é a ativação do metabolismo basal, contribuindo de forma importante com a regulação do peso corporal, enquanto diminui os níveis plasmáticos de triglicérides e colesterol. A ativação seletiva do receptor β para o hormônio tireoideano (TR) por meio de agonistas seletivos reduziu níveis séricos de colesterol além de aumentar o metabolismo sem causar efeitos indesejáveis sobre o coração, osso ou músculo esquelético. Estes dados sugerem que estes agonistas poderiam ser úteis no tratamento das manifestações da síndrome metabólica tais como obesidade, hipercolesterolemia e resistência à insulina. Dessa forma, estudamos os efeitos da ativação do TR usando um agonista também da série GC, o GC-24, em ratos machos Wistar tratados com dieta rica em gordura e submetidos a injeções diárias de T3 correspondente a 10x a dose fisiológica (30g/g P.C./dia) ou GC-24 em dose equimolar (17g/g P.C./dia). Nosso estudo mostrou que o GC-24 preveniu algumas alterações metabólicas típicas da síndrome metabólica, tais como o aumento da massa gorda, intolerância à glicose e hipertrigliceridemia e corrigiu parcialmente outras como a hipercolesterolemia, o aumento do conteúdo de colesterol hepático e IL-6. Estes achados sugerem um papel importante do TR na mediação dos efeitos do T3 e devem ter repercussão importante na utilização potencial de agonistas seletivos ao TRβ como agentes hipocolesterolemiantes
Title in English
Role of TR in diet- induced thermogenesis
Keywords in English
metabolism
thermogenesis
thyroid hormones
TR analogs
Abstract in English
Thyroid hormone (T3) plays an important role in the development, growth and cell metabolism. One of its main effects is to activate the basal metabolic rate significantly contributing to the regulation of body weight, while decreasing serum triglycerides and cholesterol levels. Thyroid hormone receptor selective activation through selective agonists reduced serum cholesterol levels besides increasing metabolic rate without causing undesirable side effects on the heart, bone or skeletal muscle. These data suggest that these agonists could be useful in the treatment of metabolic syndrome manifestations such as obesity, hypercholesterolemia and insulin resistance. Thus, we studied the effects of TR activation also using an agonist from the GC series, the GC-24 in male Wistar rats treated with high fat diet and submitted to daily T3 injections, corresponding to 10x physiological dose (30g/g B.W. /day) or equimolar doses of GC-24 (17g/g P.C. /day). Our study has shown that GC-24 prevented some of the metabolic abnormalities typical of metabolic syndrome such as increase in fat mass, glucose intolerance and hypertriglyceridemia and partially corrected other ones like hypercholesterolemia, the increase in hepatic cholesterol and IL-6 levels. These findings suggest that TR has an important role in the mediating of T3 effects and should have important repercussions in the potential use of selective agonists to TR as cholesterol lowering agents.
 
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Publishing Date
2010-06-08
 
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