Selective activation of PPARα maintains thermogenic capacity of beige adipocytes.
iScience
; 26(7): 107143, 2023 Jul 21.
Article
em En
| MEDLINE
| ID: mdl-37456852
ABSTRACT
Beige adipocytes are inducible thermogenic adipocytes used for anti-obesity treatment. Beige adipocytes rapidly lose their thermogenic capacity once external cues are removed. However, long-term administration of stimulants, such as PPARγ and ß-adrenergic receptor agonists, is unsuitable due to various side effects. Here, we reported that PPARα pharmacological activation was the preferred target for maintaining induced beige adipocytes. Pemafibrate used in clinical practice for dyslipidemia was developed as a selective PPARα modulator (SPPARMα). Pemafibrate administration regulated the thermogenic capacity of induced beige adipocytes, repressed body weight gain, and ameliorated impaired glucose tolerance in diet-induced obese mouse models. The transcriptome analysis revealed that the E-twenty-six transcription factor ELK1 acted as a cofactor of PPARα. ELK1 was mobilized to the Ucp1 transcription regulatory region with PPARα and modulated its expression by pemafibrate. These results suggest that selective activation of PPARα by pemafibrate is advantageous to maintain the function of beige adipocytes.
Texto completo:
1
Bases de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
IScience
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão