(-)-Hydroxycitric acid alleviates oleic acid induced steatosis, oxidative stress and inflammation in primary chicken hepatocytes by regulating AMPK mediated ROS levels

Nonalcoholic fatty liver disease (NAFLD) is one of the most complex liver diseases in the world, which is characterized by hepatic steatosis, oxidative stress, inflammation, and apoptosis. (-)-Hydroxycitric acid [(-)-HCA] can regulate obesity in different animals; while these beneficial effect of (-)-HCA whether can alleviates the NAFLD and its mechanism is unclear. Hence, this study aimed to determine the potential actions and mechanisms of (-)-HCA on NAFLD in oleic acid (OA)-induced hepatocytes. We found that (-)-HCA effectively improved OA-induced hepatic steatosis by regulating expression level of fat metabolism key factors, which achieved through activating AMP-activated protein kinase (AMPK) signaling in hepatocytes. Importantly, activated AMPK alleviates mitochondrial disorder via peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) -nuclear transcription factor 1 (NRF-1) -mitochondrial transcription factor A (TFAM) pathway, and then reduces ROS production and blocking the activation of p38 MAPK- NF-κB pathway in OA-induced hepatocytes. These results not only provide a theoretical basis for the occurrence and development of NAFLD, but also offer compelling evidence for prevention of NAFLD supplemental with (-)-HCA.