Short- and Medium-Chain Fatty Acid Profiles in Biopsy-Proven Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study
10 affiliations
- 1Obesity, Diabetes and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
- 2Department of Endocrinology and Nutrition, Virgen de la Arrixaca University Hospital, 30120 Murcia, Spain
- 3Department of Endocrinology and Nutrition, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga and Nanomedicine Platform (IBIMA-Plataforma BIONAND), 29010 Málaga, Spain
- 4Department of Anatomy and Comparative Pathology, Faculty of Veterinary Science, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain
- 5Facility of Innovation and Analysis in Animal Source Foodstuffs of SAIUEx, University of Extremadura, 10003 Cáceres, Spain
- 6Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
- 7ImmunoBiota Therapeutics Pty Ltd., Melbourne 3187, Australia
- 8Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, 30120 Murcia, Spain
- 9Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
- 10Department of Medicine and Dermatology, Faculty of Medicine, University of Malaga, 29071 Malaga, Spain
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic liver disease with increasing prevalence worldwide. Increasing evidence suggests that short-chain fatty acids (SCFAs) play an important role in MASLD. Medium-chain fatty acids (MCFAs), although less studied, may also contribute to MASLD pathogenesis. The aim of this study was to evaluate plasma SCFA and MCFA profiles across the MASLD histological spectrum and their associations with clinical, biochemical, and histopathological features of disease severity. Methods: We included 115 adults with obesity undergoing bariatric surgery. Intraoperative liver biopsies were assessed using the Steatosis, Activity, Fibrosis (SAF) score. Participants were classified as no MASLD (n = 26), metabolic dysfunction-associated steatotic liver (MASL; n = 42), or metabolic dysfunction-associated steatohepatitis (MASH; n = 47). Six SCFAs and two MCFAs were quantified in plasma by liquid chromatography–mass spectrometry. Results: Patients with MASH showed lower acetate and higher hexanoate plasma levels than those without MASLD. Acetate was inversely associated with ALT, AST, GGT, glucose, HbA1c, cytokeratin-18, SAF score, steatosis and lobular inflammation, whereas hexanoate was positively associated with SAF score and lobular inflammation. Higher acetate concentrations were independently associated with lower odds of MASH (OR 0.973; p = 0.040), while ALT levels were independently associated with increased odds of MASH (OR 1.083, p = 0.001). Conclusions: MASH in patients with obesity is characterized by a distinct circulating fatty acid profile, with reduced acetate and increased hexanoate. Lower acetate levels were independently associated with MASH and markers of metabolic and histological disease severity.
Related
- Additive interaction between ultrasound-diagnosed metabolic dysfunction-associated steatotic liver disease and hyperuricemia on impaired fasting glucose: a large-scale cross-sectional study
- Sex differences in the prevalence of metabolic dysfunction-associated steatotic liver disease in hospitalized patients: a single-center cross-sectional study
- Th17/Treg imbalance and clinical characteristics in psoriasis patients with metabolic dysfunction-associated steatotic liver disease: a cross-sectional analysis
- Efficacy and safety of GLP-1 receptor agonists in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) : A systematic review and meta-analysis
- Efficacy of plant extracts for metabolic dysfunction-associated steatotic liver disease: a network meta-analysis
BibTeX
@article{rosmadrid2026short,
title = {{Short- and Medium-Chain Fatty Acid Profiles in Biopsy-Proven Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study}},
author = {Inmaculada Ros-Madrid and María A. Martínez-Sánchez and Rosario P. Cano-Mármol and Sara Rico-Chazarra and Lidia Sánchez-Alcoholado and Virginia E. Fernández-Ruiz and Alicia González-González and Carlos M. Martínez and Antonio Silva and Esteban N. Gurzov and Eliana Mariño and María D. Frutos and Mercedes Ferrer-Gómez and José C. Fernández-García and María Á. Núñez-Sánchez and Bruno Ramos-Molina},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213548},
url = {https://www.mdpi.com/2072-6643/18/21/3548},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Short- and Medium-Chain Fatty Acid Profiles in Biopsy-Proven Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study
AU - Inmaculada Ros-Madrid
AU - María A. Martínez-Sánchez
AU - Rosario P. Cano-Mármol
AU - Sara Rico-Chazarra
AU - Lidia Sánchez-Alcoholado
AU - Virginia E. Fernández-Ruiz
AU - Alicia González-González
AU - Carlos M. Martínez
AU - Antonio Silva
AU - Esteban N. Gurzov
AU - Eliana Mariño
AU - María D. Frutos
AU - Mercedes Ferrer-Gómez
AU - José C. Fernández-García
AU - María Á. Núñez-Sánchez
AU - Bruno Ramos-Molina
PY - 2026
DA - 2026/10/28
JO - Nutrients
DO - 10.3390/nu18213548
UR - https://www.mdpi.com/2072-6643/18/21/3548
AB - Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic liver disease with increasing prevalence worldwide. Increasing evidence suggests that short-chain fatty acids (SCFAs) play an important role in MASLD. Medium-chain fatty acids (MCFAs), although less studied, may also contribute to MASLD pathogenesis. The aim of this study was to evaluate plasma SCFA and MCFA profiles across the MASLD histological spectrum and their associations with clinical, biochemical, and histopathological features of disease severity. Methods: We included 115 adults with obesity undergoing bariatric surgery. Intraoperative liver biopsies were assessed using the Steatosis, Activity, Fibrosis (SAF) score. Participants were classified as no MASLD (n = 26), metabolic dysfunction-associated steatotic liver (MASL; n = 42), or metabolic dysfunction-associated steatohepatitis (MASH; n = 47). Six SCFAs and two MCFAs were quantified in plasma by liquid chromatography–mass spectrometry. Results: Patients with MASH showed lower acetate and higher hexanoate plasma levels than those without MASLD. Acetate was inversely associated with ALT, AST, GGT, glucose, HbA1c, cytokeratin-18, SAF score, steatosis and lobular inflammation, whereas hexanoate was positively associated with SAF score and lobular inflammation. Higher acetate concentrations were independently associated with lower odds of MASH (OR 0.973; p = 0.040), while ALT levels were independently associated with increased odds of MASH (OR 1.083, p = 0.001). Conclusions: MASH in patients with obesity is characterized by a distinct circulating fatty acid profile, with reduced acetate and increased hexanoate. Lower acetate levels were independently associated with MASH and markers of metabolic and histological disease severity.
SN - 2072-6643
ER -