Ganoderma Lucidum Protects Against Liver Damage From High-fat Diets

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Background and objectives

A semipermanent high-fat fare (HFD) exerts lipotoxic effects connected aggregate organs, peculiarly nan liver, starring to metabolic diseases. This study aimed to delineate nan move effects of HFD connected lipid metabolism, elucidate nan mechanisms underlying hepatic lipotoxicity, and analyse nan protective effects of Ganoderma lucidum against lipotoxicity both in vitro and in vivo.

Methods

C57BL/6 mice were fed either a 45% aliases 60% HFD, followed by measurements of assemblage composition, serum lipid profile, and liver pathology astatine four, eight, twelve, and sixteen weeks. Inflammatory responses, nan unfolded macromolecule consequence (UPR), and endoplasmic reticulum (ER)-phagy were examined successful nan livers of mice astatine 16 weeks. Male C57BL/6 mice were randomly assigned to 4 groups (n = 12 per group): normal diet, 45% HFD, and 2 HFD + Ganoderma lucidum water extract (GLE) groups (1 g/kg/d and 2 g/kg/d of crude drug, orally administered by gavage for 8 weeks pursuing a four-week HFD induction).

Results

Body weight, assemblage fat, serum lipids, and hepatic steatosis accrued progressively, accompanied by impaired glucose tolerance and liver injury, arsenic indicated by elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. HFD besides induced activation of nan STING and NF-κB signaling pathways, arsenic good arsenic nan PERK and IRE1 branches of nan UPR. Similarly, ER-phagy selective receptors, peculiarly FAM134B, which is chiefly expressed successful hepatocytes arsenic shown by single-cell sequencing, were upregulated aft 16 weeks of HFD feeding. Furthermore, GLE mitigated palmitic acid-induced lipotoxicity successful superior hepatocytes, arsenic evidenced by improved compartment viability, reduced ALT, AST, and lactate dehydrogenase levels successful nan civilization supernatant, and decreased transferase dUTP nick-end labeling-positive compartment counts. In 45% HFD-fed mice, GLE reduced serum full cholesterol, low-density lipoprotein, and hepatic triglyceride levels.

Conclusions

HFD-induced lipotoxicity causes hepatic insubstantial wounded and inflammatory responses, which whitethorn beryllium alleviated by coordinated regularisation of compensatory UPR and ER-phagy. Ganoderma lucidum shows committedness arsenic a dietary supplement for managing metabolic disorders.

Source:

Journal reference:

Cao, C., et al. (2025). Ganoderma lucidum Alleviates High-fat Diet-induced Hepatic Lipotoxicity via Modulating nan Unfolded Protein Response and Endoplasmic Reticulum-phagy. Future Integrative Medicine. doi.org/10.14218/fim.2025.00031

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