Miquelianin in Folium Nelumbinis extract promotes white-to-beige fat conversion via blocking AMPK/DRP1/mitophagy and modulating gut microbiota in HFD-fed mice

Wang, Z., Yang, T., Zeng, M., Wang, Z., Chen, Q., Chen, J., Christian, M. ORCID: 0000-0002-1616-4179 and He, Z., 2023. Miquelianin in Folium Nelumbinis extract promotes white-to-beige fat conversion via blocking AMPK/DRP1/mitophagy and modulating gut microbiota in HFD-fed mice. Food and Chemical Toxicology, 181: 114089. ISSN 0278-6915

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Abstract

The main purpose of the present study was to investigate the effect of miquelianin (quercetin 3-O-glucuronide, Q3G), one of the main flavonoids in the Folium Nelumbinis extract (FNE), on beige adipocyte formation and its underlying mechanisms. In 3T3-L1 adipocytes Q3G (12.8%)-rich FNE treatment upregulated beige-related markers such as SIRT1, COX2, PGC-1α, TFAM, and UCP1. Furthermore, Q3G enhanced mitochondrial biosynthesis and inhibited mitophagy by downregulating the expression of PINK1, PARKIN, BECLIN1 and LC-3B in 3T3-L1 cells. Moreover, in high-fat-diet (HFD)-fed mice, Q3G markedly inhibited body weight gain, reduced blood glucose/lipid levels, reduced white adipose tissues (WAT) and mitigated hepatic steatosis. Meanwhile, the induced beiging accompanied by suppressed mitophagy was also demonstrated in inguinal WAT (iWAT). Chemical intervention of AMPK activity with Compound C (Com C) and Acadesine (AICAR) revealed that AMPK/DRP1 signaling was involved in Q3G-mediated mitophagy and the beiging process. Importantly, 16S rRNA sequencing analysis showed that Q3G beneficially reshaped gut microbiota structure, specifically inhibiting unclassified_Lachnospiraceae, Faecalibaculum, Roseburia and Colidextribacter while increasing Bacteroides, Akkermansia and Mucispirillum, which may potentially facilitate WAT beiging. Collectively, our findings provide a novel biological function for Folium Nelumbinis and Q3G in the fight against obesity through activating the energy-dissipating capacity of beige fat.

Item Type:	Journal article
Publication Title:	Food and Chemical Toxicology
Creators:	Wang, Z., Yang, T., Zeng, M., Wang, Z., Chen, Q., Chen, J., Christian, M. and He, Z.
Publisher:	Elsevier BV
Date:	November 2023
Volume:	181
ISSN:	0278-6915
Identifiers:	Number Type 10.1016/j.fct.2023.114089 DOI 1818128 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Jeremy Silvester
Date Added:	11 Oct 2023 10:13
Last Modified:	11 Oct 2023 10:13
URI:	https://irep.ntu.ac.uk/id/eprint/49954

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