Therapeutic effects of chitooligosaccharide-epigallocatechin gallate conjugate on NAFLD: impact on gut-liver axis, lipid metabolism, and inflammation in rats fed a high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder correlated with hepatic lipid homeostasis, gut dysbiosis, and inflammation. In this study, we propose a novel dietary therapy for NAFLD utilizing a conjugate of chitooligosaccharide (COS) and epigallocatechin gallate (EGCG), as the underlying mechanisms of NAFLD remain unclear. NAFLD was induced in male Wistar rats by administering a high-fat diet (HFD) for 16 weeks, followed by administration of COS-EGCG conjugate (150, 300, and 600 mg/kg) for an additional four weeks. The treatment alleviated metabolic parameters, liver steatosis, and injury. It also reduced hepatic lipid accumulation by downregulating the expression of CD36, fatty acid synthase (FASN), and sterol regulatory element-binding protein 1c (SREBP-1c), while upregulating peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1 A (CPT1A), and microsomal triglyceride transfer protein (MTTP). Regarding the gut-liver axis, the conjugate modulated gut microbiota, reduced serum lipopolysaccharide (LPS) levels, and restored the expression of intestinal tight junction proteins (zonula occludens-1; ZO-1 and occludin). It also prevented liver inflammation induced by gut-derived LPS by suppressing the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. The results suggest that the COS-EGCG conjugate exerts therapeutic effects against NAFLD by regulating hepatic lipid metabolism, modulating the gut microbiota, and attenuating gut-derived LPS-induced liver inflammation.