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- W4307922525 abstract "Pharmacological intervention to induce browning of white adipose tissue provides a promising anti-obesity therapy. The fruits of Garcinia cambogia (Clusiaceae) have been widely applied to manage body weight; however, the chemical principles remain unclear. The current study aims to discover browning inducers from the fruits of G. cambogia and investigate the underlying mechanisms.The bioactivity-based molecular networking and Oil Red O staining on 3T3-L1 and C3H10T1/2 adipocytes were applied for guided isolation. High-fat diet-induced obese mice were recruited to evaluate the anti-obesity activity.The bioactivity-based molecular networking-guided isolation yielded several polycyclic polyprenylated acylphloroglucinols from the fruits of G. cambogia with lipid-lowering effect in adipocytes, including guttiferone J (GOJ), garcinol and 14-deoxygarcinol. As the most potent one, GOJ (10 μM) reduced lipid accumulation by 70% and 76% in 3T3-L1 and C3H10T1/2 adipocytes, respectively. Furthermore, GOJ (2.5-10 μM) increased the expression of the deacetylase sirtuin 3 (SIRT3) and activated it, which, in turn, reduced the acetylation level of PPARγ coactivator-1α to boost mitochondrial biogenesis and promoted uncoupling protein 1 expression to enhance thermogenesis, resulting in browning of adipocytes. In high-fat diet-induced-obese mice, GOJ (10 and 20 mg·kg-1 ·day-1 for 12 weeks) protected against adiposity, hyperlipidaemia, insulin resistance and liver lipotoxicity, through boosting SIRT3-mediated browning of inguinal adipose tissue.GOJ represents a new scaffold of thermogenic inducer, which is responsible for the anti-obesity property of G. cambogia and can be further developed as a candidate for treating obesity and its related disorders." @default.
- W4307922525 created "2022-11-06" @default.
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- W4307922525 date "2022-11-22" @default.
- W4307922525 modified "2023-10-15" @default.
- W4307922525 title "Bioactivity‐based molecular networking‐guided identification of guttiferone J from <i>Garcinia cambogia</i> as an anti‐obesity candidate" @default.
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- W4307922525 doi "https://doi.org/10.1111/bph.15979" @default.
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