RESUMO
The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Bege/efeitos dos fármacos , Adipócitos Bege/metabolismo , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Alcaloides Indólicos/farmacologia , Quinazolinas/farmacologia , Fatores de Transcrição/metabolismo , Adipócitos Bege/citologia , Adipócitos Brancos/citologia , Animais , Produtos Biológicos/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Termogênese/genética , Termogênese/fisiologiaRESUMO
The fluorescence characteristics of various New Zealand honeys were investigated to establish if this technique might detect signatures unique to manuka (Leptospermum scoparium) and kanuka (Kunzea ericoides) honeys. We found unique fluorescence profiles for these honeys which distinguished them from other New Zealand honey floral types. Two excitation-emission (ex-em) marker wavelengths each for manuka and kanuka honeys were identified; manuka honey at 270-365 (MM1) and 330-470 (MM2) nm and kanuka honey at 275-305 (KM1) and 445-525 (KM2) nm. Dilution of manuka and kanuka honeys with other honey types that did not possess these fluorescence profiles resulted in a proportional reduction in fluorescence signal of the honeys at the marker wavelengths. By comparison, rewarewa (Knightia excelsa), kamahi (Weinmannia racemosa), and clover (Trifolium spp.) honeys did not exhibit unique fluorescence patterns. These findings suggests that a fluorescence-based screening approach has potential utility for determining the monoflorality status of manuka and kanuka honeys.