Role of sympathetic innervation in obesity

Bibliographic Details
Main Author: Pereira, Mafalda Maria Robalo de Azevedo Aleixo
Publication Date: 2015
Format: Master thesis
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/15841
Summary: Part of the results presented in this thesis were published in the following reference (DOI 10.1016/j.cell.2015.08.055): Wenwen Zeng*, Roksana M. Pirzgalska*, Mafalda M.A. Pereira, Nadiya Kubasova, Andreia Barateiro, Elsa Seixas, Yi-Hsueh Lu, Albina Kozlova, Henning Voss, Gabriel G. Martins, Jeffrey M. Friedman and Ana I. Domingos. Sympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis. Cell 163, 84-94 (2015). The work was also presented through poster presentations at iMED Conference 6.0 (Lisbon, 2014), Sociedade Portuguesa de Bioquímica Meeting (Coimbra, 2014) and Sociedade Portuguesa de Neurociências Meeting (Póvoa de Varzim, 2015).
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spelling Role of sympathetic innervation in obesityObesitySympathetic nervous systemPEGylationAmphetamineAnatomyAdipose organDomínio/Área Científica::Engenharia e Tecnologia::Engenharia QuímicaPart of the results presented in this thesis were published in the following reference (DOI 10.1016/j.cell.2015.08.055): Wenwen Zeng*, Roksana M. Pirzgalska*, Mafalda M.A. Pereira, Nadiya Kubasova, Andreia Barateiro, Elsa Seixas, Yi-Hsueh Lu, Albina Kozlova, Henning Voss, Gabriel G. Martins, Jeffrey M. Friedman and Ana I. Domingos. Sympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis. Cell 163, 84-94 (2015). The work was also presented through poster presentations at iMED Conference 6.0 (Lisbon, 2014), Sociedade Portuguesa de Bioquímica Meeting (Coimbra, 2014) and Sociedade Portuguesa de Neurociências Meeting (Póvoa de Varzim, 2015).Obesity is considered a world epidemic, but no efficient therapy is available so far. Besides, the anatomy of the adipose organ was not described in detail. Thus, different mechanisms were proposed to explain obesity condition. One of those is the MONA LISA hypothesis that states that Most Obesities kNown Are Low In Sympathetic Activity. However, this theory is based on measurements of norepinephrine decrease in the heart and there is no direct evidence of the role of sympathetic nervous system (SNS) in obesity. In this work, PEGyDT-mediated sympathectomy was developed to specifically ablate the SNS, without affecting the central nervous system. This was achieved by PEGylation of diphtheria toxin, a strategy that is approved by Food and Drug Administration and used to modulate pharmacokinetics of several biopharmaceuticals clinically approved. The results show that sympathectomy leads to irreversible obesity, without affecting food intake. SNS ablation also causes glucose tolerance and thermogenesis impairment. Moreover, it was discovered that the SNS is required for amphetamine effects and this is an additional mechanism of action for this anti-obesity drug, as it was thought that it had an exclusive effect in the brain to suppress appetite. Furthermore, the anatomy of adipose organ was revealed in detail using optical projection tomography coupled to tissue clearing. It was shown that not only the inguinal adipose organ contains nerve bundles and a network of vasculature, but also that in the proximity of these structures there is a lymph node. In the epididymal fat, granular substructures are present but not nerve bundles or lymph node. In conclusion, a strategy to study the role of the SNS in obesity was developed and causality of MONA LISA hypothesis was demonstrated. Moreover, an additional mechanism of action for amphetamine was shown and neuroanatomy of adipose organs was described for the first time.Domingos, AnaBernardes, GonçaloRUNPereira, Mafalda Maria Robalo de Azevedo Aleixo2015-11-16T16:56:56Z2015-092015-112015-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/15841enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:19:45Zoai:run.unl.pt:10362/15841Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T16:50:40.917702Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Role of sympathetic innervation in obesity
title Role of sympathetic innervation in obesity
spellingShingle Role of sympathetic innervation in obesity
Pereira, Mafalda Maria Robalo de Azevedo Aleixo
Obesity
Sympathetic nervous system
PEGylation
Amphetamine
Anatomy
Adipose organ
Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química
title_short Role of sympathetic innervation in obesity
title_full Role of sympathetic innervation in obesity
title_fullStr Role of sympathetic innervation in obesity
title_full_unstemmed Role of sympathetic innervation in obesity
title_sort Role of sympathetic innervation in obesity
author Pereira, Mafalda Maria Robalo de Azevedo Aleixo
author_facet Pereira, Mafalda Maria Robalo de Azevedo Aleixo
author_role author
dc.contributor.none.fl_str_mv Domingos, Ana
Bernardes, Gonçalo
RUN
dc.contributor.author.fl_str_mv Pereira, Mafalda Maria Robalo de Azevedo Aleixo
dc.subject.por.fl_str_mv Obesity
Sympathetic nervous system
PEGylation
Amphetamine
Anatomy
Adipose organ
Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química
topic Obesity
Sympathetic nervous system
PEGylation
Amphetamine
Anatomy
Adipose organ
Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química
description Part of the results presented in this thesis were published in the following reference (DOI 10.1016/j.cell.2015.08.055): Wenwen Zeng*, Roksana M. Pirzgalska*, Mafalda M.A. Pereira, Nadiya Kubasova, Andreia Barateiro, Elsa Seixas, Yi-Hsueh Lu, Albina Kozlova, Henning Voss, Gabriel G. Martins, Jeffrey M. Friedman and Ana I. Domingos. Sympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis. Cell 163, 84-94 (2015). The work was also presented through poster presentations at iMED Conference 6.0 (Lisbon, 2014), Sociedade Portuguesa de Bioquímica Meeting (Coimbra, 2014) and Sociedade Portuguesa de Neurociências Meeting (Póvoa de Varzim, 2015).
publishDate 2015
dc.date.none.fl_str_mv 2015-11-16T16:56:56Z
2015-09
2015-11
2015-09-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/15841
url http://hdl.handle.net/10362/15841
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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