Regulatory effects and mechanisms of exopolysaccharides from Lactococcus lactis Z-2 on lipid metabolism in common carp (Cyprinus carpio) fed a high-fat diet

Int J Biol Macromol. 2025 Jun 24:145528. doi: 10.1016/j.ijbiomac.2025.145528. Online ahead of print.

Abstract

Building on prior research demonstrating the immunomodulatory, antioxidant, and disease-resistant properties of exopolysaccharides (EPS) from Lactococcus lactis Z-2 in fish, this study investigates their regulatory mechanisms on lipid metabolism in Cyprinus carpio. An in vitro high-fat model was established through oleic acid (OA) induction, revealing that both extracellular products (ECP) and EPS significantly reduced key lipid parameters (TG, TC, LDL-C) and down-regulated lipid synthesis genes (fas, srebp, acc, acly) within non-cytotoxic concentrations. Concurrently, these treatments increased HDL-C and enhanced expression of lipolytic regulators (lpl, hsl, pparα, cpt-1, atgl) and alleviated hepatocellular damage. Pharmacological inhibition of PKA signaling completely abrogated these metabolic effects, establishing the pathway's essential role in mediating ECP/EPS activity. In vivo validation demonstrated EPS's capacity to: 1) Improve intestinal morphogenesis and counteract high-fat diet (HFD)-induced villus atrophy. 2) Attenuate hepatic steatosis and serum lipid dysregulation. 3) Up-regulate lipid catabolism genes and down-regulate lipid synthesis genes across multiple tissues (intestine, hepatopancreas, muscle). These multimodal effects position EPS as a promising therapeutic candidate for managing HFD-associated metabolic disorders in aquaculture species.

Keywords: Cyprinus carpio; Exopolysaccharide; Lipid metabolism.