PKC-δ-dependent mitochondrial ROS attenuation is involved as 9-OAHSA combats lipoapotosis in rat hepatocytes induced by palmitic acid and in Syrian hamsters induced by high-fat high-cholesterol high-fructose diet

Metabolic-associated fatty liver disease (MAFLD) is a global concern, often undetected until reaching an advanced stage. Palmitic acid (PA) is a type of fatty acid that increases and leads to liver apoptosis in MAFLD. However, there is currently no approved therapy or compound for MAFLD. Recently, branched fatty acid esters of hydroxy fatty acids (FAHFAs), a group of bioactive lipids, have emerged as promising agents to treat asso-ciated metabolic diseases. This study utilizes one type of FAHFA, oleic acid ester of 9-hydroxystearic acid (9-OAHSA), to treat PA-induced lipoapoptosis in an in vitro MAFLD model using rat hepatocytes and a high-fat high-cholesterol high-fructose (HFHCHFruc) diet in Syrian hamsters. The results indicate that 9-OAHSA res-cues hepatocytes from PA-induced apoptosis and attenuates lipoapoptosis and dyslipidemia in Syrian hamsters. Additionally, 9-OAHSA decreases the generation of mitochondrial reactive oxygen species (mito-ROS) and sta-bilizes the mitochondrial membrane potential in hepatocytes. The study also demonstrates that the effect of 9-OAHSA on mito-ROS generation is at least partially mediated by PKC-delta signaling. These findings suggest that 9-OAHSA shows promise as a therapy for MAFLD.

Automated summary

Metabolic-associated fatty liver disease (MAFLD) is a global concern that often goes unnoticed until it reaches an advanced stage. Palmitic acid (PA) is implicated in liver apoptosis in MAFLD, but there is currently no approved therapy. This study investigates the potential of a bioactive lipid called oleic acid ester of 9-hydroxystearic acid (9-OAHSA) to treat PA-induced lipoapoptosis in an in vitro MAFLD model and a high-fat high-cholesterol high-fructose diet in Syrian hamsters. The findings suggest that 9-OAHSA rescues hepatocytes from apoptosis, improves dyslipidemia, and stabilizes mitochondrial function, making it a promising therapy for MAFLD.