Abstract: This study established a mouse model of metabolic-associated fatty liver disease (MAFLD) induced by a high-fat diet and then treated it with Suaeda salsa polysaccharides. The effects of S. salsa polysaccharides on the animal’s general health, liver histopathology, serum lipid metabolism-related indicators, serum inflammatory cytokines, and programmed necrosis were evaluated. The results showed that compared with the control group, the model group showed significantly increased body mass and liver index. Hematoxylin & eosin (HE) staining revealed significant hepatic steatosis in the model group. Oil Red O staining showed a large amount of lipid accumulation in the hepatocytes of mice from the model group. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) increased, while the level of high-density lipoprotein (HDL) decreased. In liver tissue, the contents of TC and TG, the relative expression levels of sterol regulatory element binding protein 1 (SREBP1), fatty acid transporter CD36, receptor-interacting protein kinase 3 (RIP3), phospho-mixed lineage kinase domain-like protein (p-MLKL), and the relative mRNA expression levels of SREBP1, CD36, RIP3, and MLKL increased, while the relative mRNA expression levels of peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ decreased. Compared with the model group, body mass and liver index decreased in the intervention groups. Liver pathological damage was significantly attenuated; the area of lipid droplets in the liver was reduced; serum levels of TC, TG, LDL, ALT, AST, TNF-α, IL-1β, and IL-6 decreased, while HDL levels increased. The contents of TC and TG, the protein expression levels of SREBP1, CD36, RIP3, and p-MLKL, and the relative mRNA expression levels of SREBP1, CD36, RIP3, and MLKL in liver tissue decreased, while the relative mRNA expression levels of PPAR-α and PPAR-γ increased. Our findings suggest that S. salsa polysaccharides significantly alleviate high-fat diet-induced liver injury, possibly by regulating the release of inflammatory cytokines and reducing hepatic programmed necrosis, thereby mitigating MAFLD progression.

Key words: Suaeda salsa; high-fat diet; metabolic-associated fatty liver disease; necroptosis; receptor interacting protein kinase 3; mixed lineage kinase domain-like protein