O039 - SHORT CHAIN FATTY ACIDS ALTERATIONS IN PLASMA OF PATIENTS WITH SEVERE OBESITY AND BIOPSY-PROVEN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE

O039

SHORT CHAIN FATTY ACIDS ALTERATIONS IN PLASMA OF PATIENTS WITH SEVERE OBESITY AND BIOPSY-PROVEN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE

I. Ros Madrid^1,*, R.-P. Cano Mármol¹, M. A. Martínez Sánchez², S. Rico Chazarra³, V. E. Fernández-Ruíz², C. M. Martínez³, A. Silva⁴, A. Balaguer Román², M. D. Frutos⁵, M. Ferrer Gómez¹, M. Á. Nuñez Sánchez³, B. Ramos Molina³

¹Endocrinology and nutrition, ²Virgen de la Arrixaca Hospital, ³Instituto Murciano de investigación biosanitaria, Murcia, ⁴Extremadura university, Extremadura, ⁵Surgery, Virgen de la Arrixaca Hospital, Murcia, Spain

Rationale: Short-chain fatty acids (SCFAs), key metabolites produced by dietary fiber fermentation, regulate metabolic pathways involved in obesity-related disorders, including metabolic-associated steatotic liver disease (MASLD). However, data on circulating SCFAs in patients with biopsy-proven MASLD are limited. This study aimed to evaluate circulating SCFA profiles according to MASLD severity in patients with obesity and to investigate the effects of specific SCFAs in a human liver organoid (HLO) model of MASLD.

Methods: In a prospective cohort of 115 adults with obesity undergoing bariatric surgery, MASLD severity was assessed by liver histology and classified as no MASLD, simple steatosis, or metabolic dysfunction–associated steatohepatitis (MASH). Plasma acetate, propionate, butyrate, isobutyrate, valerate, and isovalerate were quantified by liquid chromatography–mass spectrometry. HLOs derived from MASLD patients were exposed to palmitic acid to mimic lipotoxic conditions, with or without acetate supplementation. Statistical analyses included Kruskal–Wallis, chi-square and Spearman correlation.

Results: Patients with MASH exhibited significantly lower plasma acetate and propionate levels compared with those without MASLD or with simple steatosis. Acetate levels were inversely associated with transaminases, glycemic parameters, cytokeratin-18 (CK-18), hepatic steatosis, and lobular inflammation. Lower acetate levels and higher alanine aminotransferase independently predicted MASH. In HLOs, acetate attenuated palmitic acid–induced lipotoxicity, as evidenced by reduced CK-18 release into the medium.

Conclusion: Alterations in circulating acetate are associated with MASLD severity and may contribute to MASH pathophysiology. These findings support a protective role for acetate in metabolic liver injury and highlight its potential as a therapeutic target.

Disclosure of Interest: None declared