Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects
| Main Author: | |
|---|---|
| Publication Date: | 2020 |
| Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10451/49187 |
Summary: | © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| id |
RCAP_9dcfa0a2e2b99b6b306823d16a98cc9d |
|---|---|
| oai_identifier_str |
oai:repositorio.ulisboa.pt:10451/49187 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| repository_id_str |
https://opendoar.ac.uk/repository/7160 |
| spelling |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effectsAmphetamineHeat dissipationLipolysisObesitySympathetic-nervous-systemSympathofacilitatorsSympathomimeticsTachycardiaThermogenesisThermoregulation© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PEGyAMPH) to exclude its central action. PEGyAMPH does not enter the brain and facilitates SNS activity via theβ2-adrenoceptor, protecting mice against obesity by increasing lipolysis and thermogenesis, coupled to higher heat dissipation, which acts as an energy sink to increase energy expenditure without altering food intake or locomotor activity. Thus, we provide proof-of-principle for a novel class of exclusively peripheral anti-obesity sympathofacilitators that are devoid of any cardiovascular and brain-related side effects.This work was supported by the Fundação Para a Ciência e Tecnologia (FCT - PTDC-BIM-MET-3750-2014 and LISBOA-01-0145-FEDER-030892), the European Molecular Biology Organization (EMBO - Installation Grant 3037), the Human Frontier Science Program (HFSP - RGY0070/2016), Maratona da Saúde (Diabetes - 2016), the European Research Council (ERC-2017-COG-771431), and the Howard Hughes Medical Institute/Wellcome International research scholar award (HHMI - 208576/Z/17/Z). G.J.L.B. is a Royal Society university Research Fellow (URF\R\180019) and FCT Investigator (IF/00624/2015). B.J. and A.K. were supported by the BBSRC (BB/M027252/1/bbsrc). We also acknowledge the Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-022125), the Project EU_FT-ICR_MS, funded by the European Union Horizon 2020 research and innovation program under grant agreement no. 731077. The contribution of Y.S., M.O., and F.C. was supported by Ministerio de Ciencia, Innovación y Universidades (grants AGL2017-88801-P and RTI2018-099592-B-C21). The contribution of M.L. was supported by the Xunta de Galicia (2015-CP079 and 2016-PG068), the Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of EU (RTI2018-101840-B-I00 and BFU2015-70454-REDT/Adipoplast), the Atresmedia Corporación and the “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/HR19/52160022. I.M. (PD/BD/52437/2013), A.B. (SFRH/BPD/96794/2013), P.M.S.D.C. (SFRH/BPD/103172/2014) and S.H.V. (SFRH/BPD/81627/2011) were supported by FCT; N.M.S. (ED481B 2016/168-0) was supported by Xunta de Galicia; and E.R.P. (BES-2015-072743) was supported by Ministerio de Economía y Competitividad (MINECO).ElsevierRepositório da Universidade de LisboaMahú, InêsBarateiro, AndreiaRial-Pensado, EvaMartinéz-Sánchez, NoeliaVaz, Sandra H.Cal, Pedro M.S.D.Jenkins, BenjaminRodrigues, Tiago M.Cordeiro, CarlosCosta, Miguel F.Mendes, RaquelSeixas, ElsaPereira, Mafalda M.A.Kubasova, NadiyaGres, VitkaMorris, ImogenTemporão, CarolinaOlivares, MartaSanz, YolandaKoulman, AlbertCorzana, FranciscoSebastião, Ana MLópez, MiguelBernardes, Gonçalo J. L.Domingos, Ana I.2021-07-28T13:57:37Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49187engCell Metab. 2020 Jun 2;31(6):1120-1135.e7.1550-413110.1016/j.cmet.2020.04.0131932-7420info: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:RCAAP2025-03-17T14:36:07Zoai:repositorio.ulisboa.pt:10451/49187Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:16:44.810599Repositórios 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 |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| title |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| spellingShingle |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects Mahú, Inês Amphetamine Heat dissipation Lipolysis Obesity Sympathetic-nervous-system Sympathofacilitators Sympathomimetics Tachycardia Thermogenesis Thermoregulation |
| title_short |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| title_full |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| title_fullStr |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| title_full_unstemmed |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| title_sort |
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects |
| author |
Mahú, Inês |
| author_facet |
Mahú, Inês Barateiro, Andreia Rial-Pensado, Eva Martinéz-Sánchez, Noelia Vaz, Sandra H. Cal, Pedro M.S.D. Jenkins, Benjamin Rodrigues, Tiago M. Cordeiro, Carlos Costa, Miguel F. Mendes, Raquel Seixas, Elsa Pereira, Mafalda M.A. Kubasova, Nadiya Gres, Vitka Morris, Imogen Temporão, Carolina Olivares, Marta Sanz, Yolanda Koulman, Albert Corzana, Francisco Sebastião, Ana M López, Miguel Bernardes, Gonçalo J. L. Domingos, Ana I. |
| author_role |
author |
| author2 |
Barateiro, Andreia Rial-Pensado, Eva Martinéz-Sánchez, Noelia Vaz, Sandra H. Cal, Pedro M.S.D. Jenkins, Benjamin Rodrigues, Tiago M. Cordeiro, Carlos Costa, Miguel F. Mendes, Raquel Seixas, Elsa Pereira, Mafalda M.A. Kubasova, Nadiya Gres, Vitka Morris, Imogen Temporão, Carolina Olivares, Marta Sanz, Yolanda Koulman, Albert Corzana, Francisco Sebastião, Ana M López, Miguel Bernardes, Gonçalo J. L. Domingos, Ana I. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Mahú, Inês Barateiro, Andreia Rial-Pensado, Eva Martinéz-Sánchez, Noelia Vaz, Sandra H. Cal, Pedro M.S.D. Jenkins, Benjamin Rodrigues, Tiago M. Cordeiro, Carlos Costa, Miguel F. Mendes, Raquel Seixas, Elsa Pereira, Mafalda M.A. Kubasova, Nadiya Gres, Vitka Morris, Imogen Temporão, Carolina Olivares, Marta Sanz, Yolanda Koulman, Albert Corzana, Francisco Sebastião, Ana M López, Miguel Bernardes, Gonçalo J. L. Domingos, Ana I. |
| dc.subject.por.fl_str_mv |
Amphetamine Heat dissipation Lipolysis Obesity Sympathetic-nervous-system Sympathofacilitators Sympathomimetics Tachycardia Thermogenesis Thermoregulation |
| topic |
Amphetamine Heat dissipation Lipolysis Obesity Sympathetic-nervous-system Sympathofacilitators Sympathomimetics Tachycardia Thermogenesis Thermoregulation |
| description |
© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-07-28T13:57:37Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/49187 |
| url |
http://hdl.handle.net/10451/49187 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Cell Metab. 2020 Jun 2;31(6):1120-1135.e7. 1550-4131 10.1016/j.cmet.2020.04.013 1932-7420 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| 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 |
| _version_ |
1833601649344512000 |