Fermented Apple Juice Attenuates High-Fat Diet-Induced Metabolic Disorders by Regulating C16 and C24 Ceramides Via the AMPK Pathway

• Fermented apple juice (FAJ) attenuates high-fat diet (HFD)-induced metabolic disorders. • FAJ regulates lipid metabolites such as C16 and C24 ceramides. • C16 and C24 ceramides reduce lipid accumulation in vitro via the AMPK pathway. • The treatment of dorsomorphin counteracted the regulatory effects of C16 and C24 ceramides. High-fat diets (HFD) contribute to the development of various diseases. This study aimed to investigate the modulatory effects of fermented apple juice (FAJ) pretreated with high hydrostatic pressure on HFD. The results revealed that FAJ has the potential to regulate lipid levels in the serum and liver of HFD-fed mice by influencing lipid metabolism, particularly modulating C16 and C24 ceramides. A HFD exposure inhibited AMPK phosphorylation, which resulted in increased PPAR γ and SREBP-1 activities. FAJ supplement alleviated steatosis in HFD-fed mice, along with increasing AMPK activity. As predicted, C16 and C24 ceramides treatment regulated lipid levels and the activities of alanine aminotransferase and aspartate aminotransferase in HepG2 cells. Additionally, C16 and C24 ceramides demonstrated the potential to modulate PPAR γ , SREBP-1, and p -AMPK α /AMPK α expression. However, the administration of dorsomorphin counteracted these regulatory effects. This study highlights the potential of FAJ and ceramides to regulate lipid accumulation through the AMPK pathway.