Brain-Sparing Sympathofacilitators Mitigate Obesity without Adverse Cardiovascular Effects.
Cell Metab
; 31(6): 1120-1135.e7, 2020 06 02.
Article
em En
| MEDLINE
| ID: mdl-32402266
ABSTRACT
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 theß2-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Fármacos Antiobesidade
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Anfetamina
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Obesidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article