Tetrahydroberberrubine exhibits preventive effect on obesity by activating PGC1α-mediated thermogenesis in white and brown adipose tissue.
Biochem Pharmacol
; 226: 116381, 2024 08.
Article
de En
| MEDLINE
| ID: mdl-38909786
ABSTRACT
The escalating prevalence of obesity presents formidable challenges, necessitating the development of effective therapeutic strategies. In this study, we aimed to elucidate the preventive effects on obesity of tetrahydroberberrubine (THBru), a derivative of berberine (BBR) and to unravel its underlying mechanism. Using an obese mouse model induced by a high-fat diet (HFD), THBru was found to markedly ameliorate obesity, as evidenced by reduced body weight, decreased Lee's index, diminished fat mass in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT), alongside improved dyslipidemia. Notably, at the same dose, THBru exhibited superior efficacy compared to BBR. RNA-sequencing and gene set enrichment analysis indicated THBru activated thermogenesis, which was further confirmed in WAT, BAT, and 3T3-L1 cells. Bioinformatics analysis of RNA-sequencing data revealed the candidate gene Pgc1α, a key regulator involved in thermogenesis. Moreover, THBru was demonstrated to elevate the expression of PGC1α by stabilizing its mRNA in WAT, BAT and 3T3-L1 cells. Furthermore, PGC1α knockdown blocked the pro-thermogenic and anti-obesity action of THBru both in vivo and in vitro. This study unravels the preventive effects of THBru on obesity through the activation of PGC1α-mediated thermogenesis, thereby delineating its potential therapeutic implications for obesity and associated disorders.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Berbérine
/
Tissu adipeux brun
/
Thermogenèse
/
Cellules 3T3-L1
/
Tissu adipeux blanc
/
Alimentation riche en graisse
/
Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes
/
Souris de lignée C57BL
/
Obésité
Limites:
Animals
Langue:
En
Journal:
Biochem Pharmacol
Année:
2024
Type de document:
Article
Pays de publication:
Royaume-Uni