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Master's Dissertation
DOI
https://doi.org/10.11606/D.10.2016.tde-26112015-164155
Document
Author
Full name
Carla Nappo Tobaruela
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Felicio, Luciano Freitas (President)
Kiss, Ana Carolina Inhasz
Mori, Claudia Madalena Cabrera
Title in Portuguese
Estudo fenotípico preliminar de camundongos fêmeas Swiss espontaneamente obesas
Keywords in Portuguese
Leptinemia
Obesidade
Síndrome metabólica
Tecido adiposo
Abstract in Portuguese
A obesidade é um sério problema de saúde pública. Este estudo teve como objetivo avaliar o crescimento de camundongos fêmeas Swiss, oriundas do biotério do Departamento de Patologia da FMVZ-USP, que se tornam espontaneamente obesas, tentando identificar em que período se iniciam estas características de obesidade. Para isso, foram realizados dois experimentos: Exp. 1 - as fêmeas foram acompanhadas do dia pós-natal 303 (DPN 303) até o DPN 491; Exp. 2 - as fêmeas foram acompanhadas do DPN 1 até o DPN 240. No Exp. 1, os animais foram divididos em dois grupos: obesas (OB) e não obesas (NOB), todas receberam dieta padrão. No Exp. 2, ao completarem 21 dias de vida, as fêmeas foram divididas em 4 grupos: dieta padrão (DP), grupos DP-OB e DP-NOB e dieta hiperlipídica (DHF), grupos DHF-OB e DHF-NOB; receberam DHF somente durante a peripuberdade (DPN 21-DPN 60). Em ambos os experimentos foram realizados acompanhamento de peso corporal, acompanhamento de ingestão alimentar, medição de comprimento corporal e medição de circunferência abdominal. No DPN 470, foi realizado o teste de tolerância à insulina (TTI) e no DPN 472 o teste de tolerância oral à glicose (TTOG) nas fêmeas do Exp. 1 e da mesma forma nos DPN 230 e 232 nas fêmeas do Exp. 2. Foi realizado teste de suspensão pela cauda (TSC) nos animais do Exp. 2. Ao final dos experimentos foram realizadas dosagens séricas de triglicérides, colesterol total, AST, leptina e insulina, além das pesagens dos órgãos: gorduras gonadal e retroperitoneal, fígado, rim com adrenal e útero com ovários. Os resultados obtidos em cada experimento foram avaliados por meio de ANOVA de duas vias seguida do teste de Bonferroni e t Student, p<0,05. Em ambos os experimentos os animais obesos apresentaram maior comprimento corporal e circunferência abdominal, além de pesagem elevada dos órgãos fígado, rim e gorduras. As dosagens de leptina foram significantes para todos os animais obesos e as dosagens de triglicérides foram significantes nos grupos OB e DP-OB. No Exp. 1, houve diferença significante na resposta à insulina entre os grupos OB e NOB (TTI) e as fêmeas OB tiveram maior pico de glicemia aos 20 minutos de teste e permaneceram por mais tempo com os níveis glicêmicos elevados (TTOG); os animais do grupo OB tiveram aumento significante do ganho de peso corporal ao longo do tempo, atingindo 70g; as dosagens de AST foram significantes nos animais OB. No Exp. 2, os animais do grupo DP-OB tiveram aumento significante do ganho de peso corporal ao longo do tempo, mostrando ganho de peso elevado após o DPN 81; as dosagens de insulina foram significantes no grupo DP-OB em relação ao grupo DP-NOB; TSC não apresentou resultados significantes. Portanto, as alterações de ganho de peso elevado, maior crescimento corporal e maior circunferência abdominal podem ser observadas nas fêmeas DP-OB já no início da vida adulta. Entretanto, as alterações metabólicas aparecem somente em idade avançada (Exp. 1). Assim, mais estudos são necessários a fim de que se possa elucidar a origem das alterações fenotípicas encontradas
Title in English
Preliminary phenotypic study in spontaneously obese Swiss females mice
Keywords in English
Adipose tissue
Leptinemia
Metabolic syndrome
Obesity
Abstract in English
Obesity is a serious public health problem. This study aimed to evaluate Swiss female mice growth that were born in the Department of Pathology (FMVZ-USP) and became obesa spontaneously, trying to identify in which period these obesity signs start. Therefore, two experiments were conducted: Exp. 1 females were observed from post-natal day 303 (PND 303) to PND 491; Exp. 2 females were observed from PND 1 to PND 240. In the Exp. 1, animals were assigned to either one of two groups: obese (OB) and non-obese (NOB), where both groups received standard chow. In the Exp. 2, when females were 21 days old, they were assigned to either: standard chow (DP), DP-OB or DP-NOB groups, and high fat diet (DHF), DHF-OB and DHF-NOB groups; these animals received DHF only in the peripuberty period (PND 21- PND 60). Body weight gain, food intake, body length and abdominal circunference were measured in both experiments. In PND 470, insulin tolerance test (ITT) and PND 472 the oral glucose tolerance test (OGTT) were performed in the females from Exp. 1, and in PND 230 and PND 232, respectively, in the animals from Exp. 2. The tail suspension test (TST) was performed in the animals from Exp. 2. In the end of experiments, blood levels of triglycerides, total colesterol, AST, leptin and insulin were evaluated and the following organs were weighted: gonadal fat pad, retroperitoneal fat pad, liver, kidney including adrenals and uterus with ovaries. Results were analysed by two-way ANOVA with Bonferroni post-test and t Student test, p<0.05. Obese animals in both experiments showed bigger body length and abdominal circunference, including heavier organs such as liver, kidney and fat pads. Leptin levels were significant higher in all obese animals and triglycerides levels were significant in OB and DP-OB groups. In the Exp. 1, there was a significant diference in the response to insulin injection in between groups OB and NOB (ITT) and OB females reached higher glicemic levels 20 min after the glucose administration, keeping these levels high longer (OGTT); OB females showed a significant increase in the body weight gain over time, reaching 70g; AST levels were significant in OB animals. In the Exp. 2, animals from DP-OB group had significant higher body weight significant in the DP-OB group comparing to DP-NOB; there was no significant results in the TST. Therefore, heavier body weights, bigger body length and bigger abdominal circunference were observed in DP-OB females in the beginning of adult life. However, metabolic alterations can be detected only in late adult life (Exp. 1). Thus, more studies need to be done aiming to clarify the origin of the phenotypic alterations found here
 
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Publishing Date
2016-04-13
 
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