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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-24052012-084649
Document
Author
Full name
Renata Silvério
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Seelaender, Marilia Cerqueira Leite (President)
Campa, Ana
Colquhoun, Alison
Ferro, Emer Suavinho
Otoch, Jose Pinhata
Title in Portuguese
A modulação da lipase de triacilglicerol do adipócito (ATGL) e da perilipina 1 contribui para o aumento da lipólise em pacientes caquéticos.
Keywords in Portuguese
Lipase
Metabolismo de gordura
Neoplasias
Tecido adiposo
Abstract in Portuguese
A depleção de tecido adiposo é um marcador da caquexia. Neste contexto, o aumento na lipólise decorrente do aumento na expressão da lipase hormônio-sensível (LHS) parece ser o fator-chave. Entretanto, a contribuição das novas proteínas relacionadas à lipólise [adipose triglyceride lipase (ATGL), comparative gene identification 58 (CGI-58) e perilipina] ainda é controversa. Caracterizamos a expressão destas proteínas e de adipocinas na caquexia. Pacientes com câncer caquéticos foram investigados. Um modelo experimental foi também estudado utilizando animais portadores de tumor sacrificados no 7º (TB7) e no 14º dia (TB14) após a inoculação tumoral e controles. Foram analisados no tecido adiposo os aspectos morfológicos, morfométricos e moleculares. Verificamos nos pacientes um aumento na expressão de LHS e ATGL, concomitantemente à redução da perilipina. Nos animais TB7 verificou-se um desequilíbrio na secreção de fatores anti e pró-inflamatórios e no grupo TB14 houve redução na expressão das proteínas analisadas sugerindo comprometimento da função celular.
Title in English
Modulation of adipose triglyceride lipase (ATGL) and perilipin 1 contributes to increased lipolysis in cachectic patients.
Keywords in English
Adipose tissue
Fat metabolism
Lipase
Neoplasms
Abstract in English
Loss of fat mass is a hallmark of cachexia. It seems that an increase in lipolysis due to increased expression of hormone-sensitive lipase (HSL) is the key factor behind this effect. However, the contribution of novel proteins related to lipolysis [adipose triglyceride lipase (ATGL), comparative gene identification - 58 (CGI-58) and perilipin 1] is still controversial. We characterized the expression of those proteins and adipokines in cachexia. Subcutaneous adipose tissue from cachetic cancer patients and epidydimal pad from tumour-bearing rats was analysed. Morphological, morphometric and molecular aspects were examined. We found an increased HSL and ATGL expression and reduction in perilipin 1 content in cachectic patients. In rats, at the intermediate stage of the syndrome, there was an imbalance in the secretion of pro and anti-inflammatory factors. In terminal cachexia the expression of almost all proteins analysed was reduced in the animals, suggesting impairment of cellular function.
 
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Publishing Date
2012-06-01
 
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