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Exploring the regulatory mechanism of Sparassis latifolia polysaccharides on hepatic glucose metabolism disorders in mice based on transcriptomics

YANG Er-Chen¹, JIA Feng-Ying², ZHANG Li-Min², JIN Li-Yang², REN Dao-Qin², JIANG Yue², YUN Shao-Jun², FENG Cui-Ping^2,*

¹Department of Physical Education, Shanxi Agricultural University, Jinzhong 030801, China；²College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China

Abstract

This study aimed to investigate the effects and mechanism of Sparassis latifolia polysaccharides (SLPs) on hepatic glucose metabolism disorders induced by a high-fat diet combined with streptozotocin (STZ) in mice. A mouse model of hepatic glucose metabolism disorder was established and treated with different doses of SLPs (100, 200, and 400 mg/kg) via gavage for 8 weeks, alongside control, model, and positive control groups (metformin hydrochloride). The effects of SLPs were systematically evaluated through pyruvate tolerance tests (PTT), hepatic glycogen content measurement, liver histomorphological analysis (HE and oil red O staining), transcriptomics, and validation of key signaling pathways using RT-qPCR and Western blot. The results showed that, compared to the model group, medium and high doses of SLPs significantly reduced area under the curve (AUC) of PTT, increased hepatic glycogen content, and ameliorated liver histopathological damage and lipid accumulation in the liver. Transcriptomic analysis revealed that SLPs intervention significantly modulated differentially expressed genes related to glucose and lipid metabolism, which were enriched in signaling pathways such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O1 (FOXO1) signaling pathway. Further validation demonstrated that SLPs up-regulated mRNA expression levels of insulin-like growth factor 1 receptor (IGF1R), protein kinase B2 (AKT2), and phosphatidylinositol-3-kinase regulatory subunit 1 (PIK3R1) in the liver of mice with glucose metabolism disorders, and down-regulated the mRNA expression levels of FOXO1 and fructose-1,6-bisphosphatase 1 (FBP1). Additionally, SLPs up-regulated p-FOXO1 protein expression level and down-regulated phosphoenolpyruvate carboxykinase (PEPCK) protein expression level. These results suggest that SLPs can effectively improve hepatic glucose metabolism disorders in mice induced by a high-fat diet combined with STZ by activating the PI3K/AKT/FOXO1 signaling pathway, involving the inhibition of key gluconeogenic enzymes and promotion of glucose utilization.

Key words: Sparassis latifolia polysaccharides; glucose metabolism; liver; transcriptomics; PI3K/AKT/FOXO1 signaling pathway

Received: 　　Accepted:

Corresponding author: 冯翠萍　　E-mail:

DOI: 10.13294/j.aps.2026.0058

Citing This Article：

YANG Er-Chen, JIA Feng-Ying, ZHANG Li-Min, JIN Li-Yang, REN Dao-Qin, JIANG Yue, YUN Shao-Jun, FENG Cui-Ping. Exploring the regulatory mechanism of Sparassis latifolia polysaccharides on hepatic glucose metabolism disorders in mice based on transcriptomics. Acta Physiol Sin 2026; 78 (3): 653-664 (in Chinese with English abstract).