α-Lack-SPI Alleviates MASLD in Rats via Regulating Hepatic Lipid Accumulation and Inflammation

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health concern. Soy protein isolate (SPI) is a plant-derived protein with high nutritional value and has shown promising effects in regulating lipid metabolism and inflammation. Objectives: This study aimed to investigate the effects of an α-subunit-deficient SPI (α-lack-SPI) on MASLD and the underlying molecular mechanisms. Methods: Rats were fed with a high-fat, high-cholesterol diet (HFD) to induce MASLD. Results: The results showed that α-lack-SPI significantly reduced the levels of hepatic TG and TC, serum ALT, AST, TC, and LDL-C, and increased serum HDL-C in rats with HFD-induced MASLD. α-lack-SPI significantly attenuated hepatic steatosis and hepatocyte ballooning revealed by histopathological analysis. Meanwhile, α-lack-SPI markedly downregulated the mRNA expressions of Srebf1, Acaca, Fasn, Pcsk9, and Hmgcr, while significantly upregulating Pparα. Additionally, α-lack-SPI treatment significantly reduced the mRNA expressions of hepatic pro-inflammatory cytokines (Tnf-α, Il-1β, Il6), chemokine (Ccl2), and inflammasome component (Nlrp3), as well as the protein expression of COX-2. Conclusions: In conclusion, α-lack-SPI alleviated MASLD in HFD-fed rats probably via improving hepatic lipid metabolism and mitigating hepatic inflammation. These findings indicate that α-lack-SPI may serve as a promising nutritional intervention for MASLD management.