Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Beige adipocytes have been considered as a potential strategy in anti-obesity therapy because of its thermogenic capacity. AMP-activated protein kinase (AMPK) plays important roles in regulating adipose tissue function. C29 is a novel pyrazolone derivative with AMPK activity. In the current study, we investigated the role of C29 in the regulation of thermogenesis using differentiated adipocytes and diet-induced obese mice, and explored the mechanisms that might be involved in energy expenditure via adipocyte AMPK activation. We showed that treatment with C29 (2.5-10 μM) concentration-dependently increased thermogenesis in differentiated preadipocytes separated from inguinal white adipose tissue (iWAT), evidenced by increased expression levels of thermogenesis markers such as Ucp1, Pgc-1α, Dio2, Prdm16, Cox7a1, Cox8b, Elovl3, and Cidea, fatty acid oxidation (FAO) genes including Cpt1a, Lcad and Pparα, as well as beige-selective genes such as Cd137, Tmem26, Slc27a1, and Tbx1. In high-fat diet (HFD)-fed mice, oral administration of C29 (30 mg·kg -1 ·day -1 ) for 9 weeks alleviated HFD-induced obesity, promoted energy expenditure and modulated iWAT browning. However, these effects were not observed in adipose-specific AMPKα1/α2 knockout (AKO) mice following C29 administration. Together, this study demonstrates that C29 regulates energy balance via adipocyte AMPK. Our findings show

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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