(−)-Hydroxycitric acid regulates energy metabolism by activation of AMPK - PGC1α - NRF1 signal pathway in primary chicken hepatocytes

Abstract

As the most important bioactive substance in Garcinia cambogia, (−)-hydroxycitric acid (HCA) is widely used in food additives to regulate obesity and diabetes in animals or humans, while the mechanism is poorly understood. The purpose of this study was to elucidate the regulatory effect and mechanism of (−)-HCA in regulating glucose and lipid metabolism in chicken primary hepatocytes. The results showed that (−)-HCA obviously decreased triglyceride content through inhibiting the fatty acid synthase protein level, and enhancing the protein level of phosphorylated acetyl CoA carboxylase, enoyl coenzyme A hydratase short chain 1 and carnitine palmitoyltransferase 1A in hepatocytes. Moreover, (−)-HCA markedly enhanced the protein level of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase A and complex IV, and which led to the enhancing of glucose uptake and catabolism in hepatocytes. Importantly, the regulation of (−)-HCA on these key factors associated with lipid and glucose metabolism in hepatocytes was mainly achieved through activation of AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α-nuclear respiratory factor 1 signaling pathway. These results convincingly demonstrated the mechanism of (−)-HCA's regulating on glucose and lipid metabolism, and provided a strategy in prevention of diseases associated with glycolipid metabolic abnormalities in animals, even in humans.