Sodium alginate supplementation can alleviate non-alcoholic fatty liver disease in rats by restoring hepatic lipid metabolism and gut microbiota

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with no approved pharmacological treatments. Several studies indicate that sodium alginate (SA) may hold promising potential in the treatment of NAFLD. However, whether SA can serve as a viable therapeutic dietary intervention for NAFLD remains unclear. Therefore, the current study aimed to explore whether supplementing with SA can alleviate NAFLD by regulating liver lipid metabolism via the gut microbiota. We used histopathology analysis, serum biochemistry assays, and scanning electron microscopy to assess the therapeutic effects of SA against NAFLD. Microbiome analysis, quantification of short-chain fatty acids, and liver lipidomics were further performed to elucidate the mechanisms underlying these therapeutic effects. Our results showed that SA significantly mitigated body fat deposition, hyperlipidemia and liver injury in rats fed with the high-fat and high-cholesterol diet (HFHCD). Additionally, SA supplementation remodeled the HFHCD-induced imbalance in gut microbiota. SA treatment substantially increased the abundance of butyrate-producing bacteria, reduced lipid metabolites associated with liver steatosis, promoted glycerophospholipid metabolism, and regulated several lipid metabolism-related signaling pathways. It also restored the imbalanced expression of the sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), and carnitine palmitoyltransferase 1 (CPT1) in HFHCD-fed rats. Taken together, our results show that SA supplementation can potentially be used as a therapeutic dietary intervention for alleviating NAFLD. In addition, our findings provide a theoretical foundation for the development of SA as a nutraceutical raw agent.