{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:37:32Z","timestamp":1790876252377,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Science and Technology Program of Guangzhou, China","award":["NO.202103000089"],"award-info":[{"award-number":["NO.202103000089"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u2248 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.<\/jats:p>","DOI":"10.3390\/nu18081233","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:24:58Z","timestamp":1776176698000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Marine-Derived Chitooligosaccharide Attenuates Obesity and Metabolic Syndrome in Bama Pigs Through LXR-Mediated Cholesterol Metabolism and Gut Microbiota Modulation"],"prefix":"10.3390","volume":"18","author":[{"given":"Minchuan","family":"Zhou","sequence":"first","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Clinical Medical Department, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Lei","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihao","family":"Yan","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunhua","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of State Administration of Traditional Chinese Medicine for Production & Development of Cantonese Medicinal Materials, Guangzhou Comprehensive Experimental Station of National Industrial Technology System for Chinese Materia Medica, Guangdong Engineering Research Center of Good Agricultural Practice & Comprehensive Development for Cantonese Medicinal Materials, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-6620","authenticated-orcid":false,"given":"Zhengquan","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.7150\/ijbs.27173","article-title":"The PI3K\/AKT pathway in obesity and type 2 diabetes","volume":"14","author":"Huang","year":"2018","journal-title":"Int. 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