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Reducing Effect of Farnesylquinone on Lipid Mass in C. elegans by Modulating Lipid Metabolism

1
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
2
Institute für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(6), 336; https://doi.org/10.3390/md17060336
Received: 26 April 2019 / Revised: 23 May 2019 / Accepted: 29 May 2019 / Published: 5 June 2019
Bioassay-guided fractionation of marine-derived fungi revealed that the EtOAc fraction from the fermentation broth of a mutated fungal strain Streptomyces nitrosporeus YBH10-5 had lipid-lowering effects in HepG2 cells. Chromatographic separation of the EtOAc fraction resulted in the isolation of 11 PKS-based derivatives, including a structurally unique meroterpenoid namely nitrosporeunol H (1). The structure of compound 1 was determined by the analysis of spectroscopic data. Further bioassay resulted in farnesylquinone (2) and its analogues to exert in vivo fat-reducing effects in C. elegans worm model. The underlying mode of action of compound 2 in the context of live worms was investigated, uncovering that compound 2 enhanced the mitochondrial β-oxidation rate and changed the transcriptional level of energy metabolism genes. Additional experiments revealed that compound 2 exerted its effects in C. elegans partially through repressing FAT-5, an isoform of stearoyl-CoA desaturase (SCD) which catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids, thereafter leading to the modification of the fatty acid profile. Thus, compound 2 was suggested to be a promising lead for further optimization to treat obesity. View Full-Text
Keywords: farnesylquinone; nitrosporeunol H; C. elegans; β-oxidation; lipid-lowering effect; fatty acid profile farnesylquinone; nitrosporeunol H; C. elegans; β-oxidation; lipid-lowering effect; fatty acid profile
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Jia, X.; Xu, M.; Yang, A.; Zhao, Y.; Liu, D.; Huang, J.; Proksch, P.; Lin, W. Reducing Effect of Farnesylquinone on Lipid Mass in C. elegans by Modulating Lipid Metabolism. Mar. Drugs 2019, 17, 336.

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