Farnesol induces mitochondrial/peroxisomal biogenesis and thermogenesis by enhancing the AMPK signaling pathway in vivo and in vitro.
Pharmacol Res
; 163: 105312, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33246168
ABSTRACT
Thermogenic activation of brown adipose tissue has been considered as an obesity treatment strategy that consumes energy. In this study, we investigated whether farnesol in vivoandin vitro models induces thermogenesis and affect the activation of the mitochondria and peroxisomes, which are key organelles in activated brown adipocytes. Farnesol induced the expression of thermogenic factors such as uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1α), and PR domain zinc-finger protein 16 (PRDM16) together with the phosphorylation of AMP-activated protein kinase alpha (AMPKα) in brown adipose tissue and primary cultured brown adipocytes. Farnesol promoted lipolytic enzymes hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). We confirmed that these inductions of lipolysis by farnesol were the underlying causes of ß-oxidation activation. Farnesol also increased the expression of oxidative phosphorylation (OXPHOS) complexes and the oxygen consumption rate (OCR) and the expansion of peroxisomes. Moreover, we proved that the thermogenic activity of farnesol was dependent on AMPKα activation using Compound C inhibitor or siRNA-AMPKα knockdown. These results suggest that farnesol may be a potential agent for the treatment of obesity by inducing energy consumption through heat generation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Antiobesidade
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Termogênese
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Adipócitos Marrons
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Farneseno Álcool
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Proteínas Quinases Ativadas por AMP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article