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Master's Dissertation
DOI
https://doi.org/10.11606/D.41.2023.tde-23012024-202059
Document
Author
Full name
Amanda Santos Pardinho
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Markus, Regina Pekelmann (President)
Fernandes, Pedro Augusto Carlos Magno
Munhoz, Carolina Demarchi
Tamura, Eduardo Koji
Title in Portuguese
Controle da resposta inflamatória do tecido adiposo por melatonina: papel da citocina IL-4
Keywords in Portuguese
Citocina IL-4
Dieta rica em lipídios
Melatonina
Tecido adiposo
Abstract in Portuguese
A inflamação do tecido adiposo branco envolve respostas imunológicas e neurais com mudança do padrão metabólico, hipertrofia e hiperplasia dos adipócitos, além de invasão de neutrófilos e macrófagos de origem monocítica. Excesso de triglicérides desencadeia resposta inflamatória de forma semelhante a padrões moleculares associados a patógenos, perigo ou dano. Alimentação rica em lipídeos (HFD) por uma noite leva à ativação do eixo imune-pineal inibindo a produção de melatonina pela pineal e promovendo a síntese de melatonina por macrófagos periféricos. No tecido adiposo branco a IL-4, uma citocina produzida por eosinófilos e linfócitos, participa da ativação do metabolismo energético e controlando o aumento do tecido adiposo branco. O entendimento dos mecanismos de ação envolvidos na resposta inflamatória do tecido adiposo é relevante para criar formulações confiáveis antiobesogenica. Deste modo, esse trabalho foi realizado com o objetivo de entendermos se os efeitos antiinflamatórios da melatonina no tecido adiposo são mediados pela IL-4. Camundongos nocauteados para o gene que expressa IL-4 mantidos em HFD por sete dias, apresentaram um maior ganho de peso corporal e de tecido adiposo em um período em que obesidade ainda não está instalada. Foi verificado que a HFD promove alterações citológicas no tecido adiposo epididimal de camundongos selvagens. Observamos também, que é necessária a presença da IL-4 para que a melatonina possa atuar contra o ganho de peso causado pela HFD. Apesar de não ter havido uma confirmação destes efeitos no aumento do tecido adiposo epididimal, os dados sugerem fortemente que a melatonina atua via IL-4 protegendo contra o ganho de peso corporal.
Title in English
Control of the inflammatory response of adipose tissue by melatonin: role of the cytokine IL-4
Keywords in English
Adipose tissue
Cytokine IL-4
High-fat diet
Melatonin
Abstract in English
Inflammation of white adipose tissue involves immune and neural responses with changes in the metabolic pattern, hypertrophy and hyperplasia of adipocytes, in addition to the invasion of neutrophils and macrophages of monocytic origin. Excess triglycerides trigger an inflammatory response similar to molecular patterns associated with pathogens, danger, or harm. High-fat diet (HFD) for one night leads to activation of the pineal-immune axis, inhibiting melatonin production by the pineal and promoting melatonin synthesis by peripheral macrophages. In white adipose tissue, IL-4, a cytokine produced by eosinophils and lymphocytes, participates in activating energy metabolism and controlling the increase in white adipose tissue. Understanding the mechanisms of action involved in the inflammatory response of adipose tissue is relevant to create reliable anti-obesogenic formulations. Thus, this work was carried out with the aim of understanding whether the anti-inflammatory effects of melatonin on adipose tissue are mediated by IL-4. Mice knocked out for the gene that expresses IL-4, maintained on HFD for seven days, showed greater gain in body weight and adipose tissue in a period when obesity is not yet installed. It was found that HFD promotes cytological changes in the epididymal adipose tissue of wild-type mice. We also observed that the presence of IL-4 is necessary for melatonin to act against the weight gain caused by HFD. Although there has not been a confirmation of these effects in the increase of epididymal adipose tissue, the data strongly suggest that melatonin acts via IL-4 protecting against body weight gain.
 
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Amanda_Pardinho.pdf (1.05 Mbytes)
Publishing Date
2024-01-29
 
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