Berberine regulates cellular lipid accumulation, oxidative stress, and cell proliferation by modulating Lrrc58a in sodium palmitate-induced Zebrafish hepatocyte

Xuzhuo Wang; Ho Chong Kin Jacky; Botelho FP; Yicheng Che; Zhaochu Sun; Weina Xu; Xuzhuo Wang; Ho Chong Kin Jacky; Botelho FP; Yicheng Che; Zhaochu Sun; Weina Xu

doi:10.3934/aas.2026004

AIMS Animal Science

2026, Volume 2, Issue 1: 35-52. doi: 10.3934/aas.2026004

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Research article

Berberine regulates cellular lipid accumulation, oxidative stress, and cell proliferation by modulating Lrrc58a in sodium palmitate-induced Zebrafish hepatocyte

1.
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Dongchuan Road, 800, Shanghai 200240, China
2.
Department of Engineering, Durham University, Stockton Road, DH1 3LE, Durham, United Kingdom
3.
Faculty of Health Sciences, University of Saint Joseph, Estrada Marginal da Ilha Verde, 14-17, Macao, China
4.
Macao Observatory for Social Development, University of Saint Joseph, Estrada Marginal da Ilha Verde, 14-17, Macao, China
5.
USJ-Kong Hon Academy for Cellular Nutrition, University of Saint Joseph, Estrada Marginal da Ilha Verde, 14-17, Macao, China

Received: 01 January 2026 Revised: 19 March 2026 Accepted: 07 May 2026 Published: 19 May 2026

We aimed to explore the function of a newly gene Leucine-rich repeat-containing 58a (Lrrc58a) and investigated beberine (BBR) regulate cell physiology by altering Lrrc58a expression in zebrafish hepatocytes (ZFL). Using small interfering RNA (siRNA) interference, the effect of Lrrc58a knockdown on lipid accumulation, oxidative stress, cell apoptosis, and autophagy in ZFL were investigated. Then, four groups, control (CON), a sodium palmitate (SP) treatment group, a beberine (BBR) treatment group, and a sodium palmitate/berberine (SP+BBR) treatment group, were set. The results revealed that Lrrc58a-knockdown cells had increased lipid accumulation, ROS content, cell apoptosis, and autophagy. Compared with the control group, SP treatment suppressed Lrrc58a mRNA expression accompanied by a similar phenotype with the si-Lrrc58a group, while BBR treatment enhanced Lrrc58a mRNA expression and reversed the process. Mechanistically, Lrrc58a knockdown increased lipid accumulation by inhibiting extracellular signal-regulated kinase (ERK), enhanced ROS accumulation by activating c-Jun N-terminal kinase (JNK), and led to cell apoptosis and autophagy by inhibiting the mammalian target of rapamycin (mTOR). In conclusion, berberine may affect physiological processes such as intracellular lipid accumulation, oxidative stress, cell apoptosis, and autophagy by altering Lrrc58a gene-level changes.
- Berberine,
- Lrrc58a,
- cellular physiology and metabolism
Citation: Xuzhuo Wang, Ho Chong Kin Jacky, Botelho FP, Yicheng Che, Zhaochu Sun, Weina Xu. Berberine regulates cellular lipid accumulation, oxidative stress, and cell proliferation by modulating Lrrc58a in sodium palmitate-induced Zebrafish hepatocyte[J]. AIMS Animal Science, 2026, 2(1): 35-52. doi: 10.3934/aas.2026004

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Abstract

We aimed to explore the function of a newly gene Leucine-rich repeat-containing 58a (Lrrc58a) and investigated beberine (BBR) regulate cell physiology by altering Lrrc58a expression in zebrafish hepatocytes (ZFL). Using small interfering RNA (siRNA) interference, the effect of Lrrc58a knockdown on lipid accumulation, oxidative stress, cell apoptosis, and autophagy in ZFL were investigated. Then, four groups, control (CON), a sodium palmitate (SP) treatment group, a beberine (BBR) treatment group, and a sodium palmitate/berberine (SP+BBR) treatment group, were set. The results revealed that Lrrc58a-knockdown cells had increased lipid accumulation, ROS content, cell apoptosis, and autophagy. Compared with the control group, SP treatment suppressed Lrrc58a mRNA expression accompanied by a similar phenotype with the si-Lrrc58a group, while BBR treatment enhanced Lrrc58a mRNA expression and reversed the process. Mechanistically, Lrrc58a knockdown increased lipid accumulation by inhibiting extracellular signal-regulated kinase (ERK), enhanced ROS accumulation by activating c-Jun N-terminal kinase (JNK), and led to cell apoptosis and autophagy by inhibiting the mammalian target of rapamycin (mTOR). In conclusion, berberine may affect physiological processes such as intracellular lipid accumulation, oxidative stress, cell apoptosis, and autophagy by altering Lrrc58a gene-level changes.

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