Exploring the role of fatty acid esters of hydroxy fatty acids in metabolic dysfunction-associated steatotic liver disease in morbidly obese women

Background: Fatty acid esters of hydroxy fatty acids (FAHFAs) present potential beneficial effects that could offer valuable insights into metabolic and inflammatory diseases. However, few FAHFAs have been studied, and their role is unclear.

Aims: To assess FAHFA levels in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) associated with morbid obesity (MO) to explore the potential significance of FAHFAs under these conditions.

Methods: Using ultra-precise liquid chromatography, FAHFA serum levels were measured in 219 women, including 53 with normal weight (NW) and 166 with MO. The MO group was classified by histological diagnosis into 35 normal liver (NL), 38 simple steatosis (SS) and 93 metabolic dysfunction-associated steatohepatitis (MASH) groups.

Results: Thirty-two FAHFA isoforms from 11 families were identified. Most FAHFAs presented low levels in MO, but tLAHOAs, LAHOA-1 and OAHOA-1 increased. In MASLD, elevated tLAHPO, LAHPO-2, PAHLA-3 and PAHLA-4 levels were observed. In MASH, increased POHLA-1, tLAHPOs, LAHPO-2 and LAHLA-3 and decreased PAHSA-1, tOAHOAs, OAHSA-2 and OAHSA-3 levels were reported.

Conclusion: This study reveals novel insights into FAHFAs in a cohort of women with MO with MASLD. In MASLD, we reported only increased levels of certain FAHFAs. In MASH, we found a different profile that could be characteristic.