A new mechanism action of nuciferine to ameliorate high-fat diet-induced obesity: microbiota-dependent modulation of adipose browning and thermogenesis

Wang, Z, Xu, Q, Younis, A ORCID: https://orcid.org/0000-0002-1127-9014, Zeng, M, Wang, Z, Chen, Q, Chen, J, Dai, X, Christian, M ORCID: https://orcid.org/0000-0002-1616-4179 and He, Z, 2026. A new mechanism action of nuciferine to ameliorate high-fat diet-induced obesity: microbiota-dependent modulation of adipose browning and thermogenesis. Food Science and Human Wellness. ISSN 2213-4530

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Abstract

Nuciferine (NUC) is a major porphine alkaloid derived from Folium Nelumbinis with anti-obesity activity. Our previous in vitro findings demonstrated that the beneficial effects of NUC were associated with its induction of thermogenic fat, although the specific mechanisms of action remain to be fully elucidated. Here, our results showed that NUC (12.8 and 25.6 mg/kg/day) treatment for 12 weeks could effectively attenuate weight gain, activate brown adipose tissues (BAT), and promote browning of inguinal white adipose tissues (iWAT) in high-fat diet (HFD)-fed mice. Subsequently, the 16S rRNA sequencing showed that NUC was effective in ameliorating the HFD-induced microbiota imbalance, and the specific genera (e.g., Lachnoclostridium, Roseburia, Limosilactobacillus, Tyzzerella, Bilophila, and Weissella) correlated strongly with brown-related features in BAT and iWAT. Meanwhile, metabolomics analysis revealed that NUC significantly increased the levels of microbial metabolites such as bile acids (e.g., taurocholic acid, chenodeoxycholic acid), myristic acid, and γ-linolenic acid, which have been previously described to turn fat “brown”. Importantly, in vitro experiments provided the first evidence of N-Acetylneuraminic acid (NANA)'s potential to activate brown adipocytes. Finally, a fecal microbiota transplantation (FMT) experiment identified that NUC-induced microbial alterations could increase energy expenditure (EE), BAT activity, and iWAT browning. Collectively, our findings demonstrated that NUC effectively promoted adipose browning and enhanced thermogenesis, linked to alterations in the gut microbiota and its metabolic byproducts, offering a novel therapeutic target for addressing obesity and associated metabolic disorders.

Item Type:	Journal article
Publication Title:	Food Science and Human Wellness
Creators:	Wang, Z., Xu, Q., Younis, A., Zeng, M., Wang, Z., Chen, Q., Chen, J., Dai, X., Christian, M. and He, Z.
Publisher:	Tsinghua University Press
Date:	7 January 2026
ISSN:	2213-4530
Identifiers:	Number Type 10.26599/fshw.2025.9250867 DOI 2575665 Other
Rights:	© 2026 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	13 Feb 2026 17:04
Last Modified:	13 Feb 2026 17:04
URI:	https://irep.ntu.ac.uk/id/eprint/55277

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