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Octanoic acid (OA), a C8 medium\u2010chain fatty acid with superior ketogenic capacity, is a promising functional nutrient for sepsis intervention. This study aimed to investigate the protective effects and underlying mechanism of OA\u2010rich enteral nutrition (EN) on sepsis\u2010associated metabolic disorders. C57BL\/6 mice were subjected to lipopolysaccharide (LPS) to establish sepsis models and received OA\u2010rich EN with different concentrations; pharmacological activation of GPR81 and genetic activation of CTRP6 and p38 were used to verify the GPR81\u2010CTRP6\u2010p38 pathway. Results revealed that OA\u2010rich EN dose\u2010dependently increased serum \u03b2\u2010hydroxybutyrate levels and decreased lactate accumulation in serum and WAT, with markedly better efficacy than conventional EN. OA\u2010rich EN significantly inhibited LPS\u2010induced upregulation of GPR81, CTRP6, phosphorylated p38 and UCP1 in WAT, mitigated WAT atrophy and abnormal browning, thereby alleviating excessive energy expenditure, body weight loss, skeletal muscle dysfunction and insulin resistance. Mechanistically, activation of GPR81, CTRP6 or p38 to promote WAT browning reversed the protective effects of OA\u2010rich EN, confirming that OA\u2010rich EN alleviated metabolic disorders by suppressing WAT browning via blocking the lactate\u2010GPR81\u2010CTRP6\u2010p38 pathway. In conclusion, OA\u2010rich EN enhanced hepatic ketogenesis to reduce lactate accumulation, thereby inhibiting the GPR81\u2010CTRP6\u2010p38 pathway and suppressing pathological WAT browning, ultimately alleviating sepsis\u2010associated metabolic disorders. These findings provide a novel targeted nutritional strategy and theoretical basis for optimizing clinical nutritional support in septic patients.<\/jats:p>","DOI":"10.1002\/fsn3.72020","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:28:38Z","timestamp":1781065718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Octanoic Acid\u2010Rich Enteral Nutrition Alleviates Sepsis\u2010Associated Metabolic Disorders by Suppressing White Adipose Tissue Browning in Mice"],"prefix":"10.1002","volume":"14","author":[{"given":"Chunliang","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery Suzhou Wuzhong People's Hospital  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungen","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-6069","authenticated-orcid":false,"given":"Chun","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital of Soochow University  Suzhou 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