Abstract
BackgroundNon-alcoholic fatty liver disease (NAFLD) is caused by multiple factors including hepatic oxidative stress, lipotoxicity, and mitochondrial dysfunction. Obesity is among the risk factors for NAFLD alongside type 2 diabetes mellitus and hyperlipidemia. α- mangostin (α-MG) extracts from the pericarps of mangosteen (Garcinia mangostana Linn.) may regulate high fat diet-induced hepatic steatosis; however the underlying mechanisms remain unknown. The aim of this study was to investigate the regulatory effect of α-MG on high fat diet-induced hepatic steatosis and the underlying mechanisms related to mitochondrial functionality and apoptosis in vivo and in vitro.MethodsSprague Dawley (SD) rats were fed on either AIM 93-M control diet, a high-fat diet (HFD), or high-fat diet supplemented with 25 mg/day mangosteen pericarp extract (MGE) for 11 weeks. Thereafter, the following were determined: body weight change, plasma free fatty acids, liver triglyceride content, antioxidant enzymes (superoxide dismutase, SOD; glutathione, GSH; glutathione peroxidase, GPx; glutathione reductase GRd; catalase, CAT) and mitochondrial complex enzyme activities. In the in vitro study, primary liver cells were treated with 1 mM free fatty acid (FFA) (palmitate: oleate acid = 2:0.25) to induce steatosis. Thereafter, the effects of α-MG (10 μM, 20 μM, 30 μM) on total and mitochondria ROS (tROS, mitoROS), mitochondria bioenergetic functions, and mitochondrial pathway of apoptosis were examined in the FFA-treated primary liver cells.ResultsThe MGE group showed significantly decreased plasma free fatty acids and hepatic triglycerides (TG) and thiorbarbituric acid reactive substances (TBARS) levels; increased activities of antioxidant enzymes (SOD, GSH, GPx, GRd, CAT); and enhanced NADH-cytochrome c reductase (NCCR) and succinate-cytochrome c reductase (SCCR) activities in the liver tissue compared with HFD group. In the in vitro study, α-MG significantly increased mitochondrial membrane potential, enhanced cellular oxygen consumption rate (OCR), decreased tROS (total ROS) and mitoROS (mitochondrial ROS) levels ; reduced Ca2+ and cytochrome c (cyt c) release from mitochondria, and reduced caspases 9 and 3 activities compared with control group.ConclusionThese findings demonstrate α-MG attenuated hepatic steatosis in high fat-diet fed rats potentially through enhanced cellular antioxidant capacity and improved mitochondrial functions as well as suppressed apoptosis of hepatocytes. The findings of study represent a novel nutritional approach on the use of α-MG in the prevention and management of NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is caused by multiple factors including hepatic oxidative stress, lipotoxicity, and mitochondrial dysfunction
Mangosteen pericarps extract markedly reduced body weight gain, plasma free fatty acids (FFA) levels, hepatic triglyceride (TG) accumulation Mangosteen pericarps extract supplementation significantly decreased body weight in the mangosteen pericarp extract (MGE) group compared to high-fat diet (HFD) group (Fig. 1a)
Mangosteen pericarps extract increased hepatic antioxidant enzyme activities and reduced reactive oxygen species (ROS) in rat liver tissue Mangosteen pericarps extract treatments increased antioxidant enzymes (SOD, GSH, glutathione peroxidase (GPx), glutathione reductase (GRd), CAT) activities in the rat liver tissue in MGE group compared to HFD group (Table 1)
Summary
Non-alcoholic fatty liver disease (NAFLD) is caused by multiple factors including hepatic oxidative stress, lipotoxicity, and mitochondrial dysfunction. The aim of this study was to investigate the regulatory effect of α-MG on high fat diet-induced hepatic steatosis and the underlying mechanisms related to mitochondrial functionality and apoptosis in vivo and in vitro. Non-alcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases and its prevalence is associated with the increase in obesity and other metabolic syndrome conditions [1, 2] The hallmark of NAFLD is hepatic steatosis, which manifests as excessive triglyceride accumulation in the hepatocytes [2]. Hepatic steatosis mainly results from disrupted lipid metabolism in the hepatocytes leading to imbalance between intrahepatic triglyceride (TG) accumulation and clearance [3]. Due to the reactive nature of the ROS, the antioxidant enzyme activities are suppressed resulting in oxidative stress and hepatic cellular injury [4]
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