Marine-Derived Chitooligosaccharide Attenuates Obesity and Metabolic Syndrome in Bama Pigs Through LXR-Mediated Cholesterol Metabolism and Gut Microbiota Modulation.

Background/Objectives: Chitooligosaccharide (COS) is a marine-derived natural product obtained from shrimp and crab shells. Although its anti-inflammatory and antioxidant activities are documented, its potential effects on obesity and metabolic syndrome remain largely unclear. This study aimed to investigate the efficacy of COST (MW ≈ 1000 Da) against high-fat diet (HFD)-induced obesity and metabolic syndrome in Bama pigs. Methods: Bama pigs were fed a HFD for 12 weeks to establish an obesity model, followed by 12 weeks of oral COST administration. Serum biochemical parameters, tissue indicators, histopathology, and gene/protein expression related to cholesterol metabolism were analyzed. Fecal bile acid (BA) profiles, gut microbiota composition, and short-chain fatty acid (SCFA) levels were also examined. Results: COST treatment significantly attenuated weight gain and improved multiple components of metabolic syndrome, including insulin resistance, dyslipidemia, and inflammation. Mechanistically, COST upregulated intestinal ABCG5/ABCG8 to promote cholesterol excretion, increased ABCA1 expression in intestine and liver to enhance reverse cholesterol transport (RCT), and upregulated hepatic LDL-R to facilitate LDL-C clearance from circulation while modulating hepatic cholesterol synthesis via SREBP2 downregulation and RNF145 upregulation. These transcriptional changes were confirmed at the protein level for LXR, LDL-R, and ABCA1. Additionally, COST decreased fecal secondary BA levels, reshaped gut microbiota composition, and increased SCFA production, with significant correlations among these factors. Conclusions: COST ameliorates protective effects against HFD-induced obesity and metabolic syndrome, potentially through the regulation of cholesterol metabolism and the modulation of the gut microbiota-BA-SCFA network.