Abstract
Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by the excess accumulation of fat in the hepatocytes. It is commonly associated with severe obesity and inflammation. Free fatty acids (FFAs) are the key to regulate lipid metabolism and immune response in hepatocyte cells. This study examined the effects of AEN (alcohol extract of nutmeg, the seed of Myristica fragrans Houtt.) on the inhibition of lipid synthesis and inflammation in vitro and in vivo and on high-fat diet-induced obesity in NAFLD mice. Our results showed that AEN treatment could downregulate the expression of lipid synthesis-related genes fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and lower the lipid content of cells. AEN also inhibited FFAs-mediated inflammation-related cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) expression in cells. In a mouse model, AEN reduced the bodyweight of obese mice and improved NAFLD without affecting food intake. Further analysis revealed that AEN significantly reduced inflammation level, cholesterol and lipid accumulation, blood glucose, and other liver function indexes in mice fed with a high-fat diet. In conclusion, AEN inhibited the aggravation of obesity and inflammation by downregulating lipid-gene expression in the liver to ameliorate NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is one of the important causes of global liver disease [1], which is characterized by diffuse hepatocytes with hepatocellular ballooning, intrahepatic inflammation, Nutrients 2020, 12, 2507; doi:10.3390/nu12092507 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 2507 and progressive fibrosis [2,3,4]
Following the screening method described in previous articles, alcohol extract of nutmeg (AEN) was screened as a lipid synthesis inhibitor by Mortierella alpina ATCC32222 (MA) in 96 well plates [24]
Fatty acids can be seen to play a key role in the formation of NAFLD: On the one hand, dietary fats are fully hydrolyzed, releasing FFAs, approximately 20% of which are delivered to the liver [52]; on the other hand, the accumulation of free fatty acids in hepatocytes can produce lipotoxicity, resulting in inflammatory reactions and hepatocyte injury [53,54]
Summary
Nonalcoholic fatty liver disease (NAFLD) is one of the important causes of global liver disease [1], which is characterized by diffuse hepatocytes with hepatocellular ballooning, intrahepatic inflammation, Nutrients 2020, 12, 2507; doi:10.3390/nu12092507 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 2507 and progressive fibrosis [2,3,4]. Nonalcoholic fatty liver disease (NAFLD) is one of the important causes of global liver disease [1], which is characterized by diffuse hepatocytes with hepatocellular ballooning, intrahepatic inflammation, Nutrients 2020, 12, 2507; doi:10.3390/nu12092507 www.mdpi.com/journal/nutrients. NAFLD progression can be categorized into simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and fatty cirrhosis, cirrhosis, and even liver cancer [5,6]. The mechanisms of NAFLD progression are widely believed to have at least two components. Fat accumulation caused by lipid metabolism disorder is a common mechanism in hepatic steatosis, followed by immune cell activation and pro-inflammatory cytokine production [3,7]. Studies have shown that obese patients with NAFLD showed decreased lipid metabolism but increased fatty acid biosynthesis [8].The increase of lipolytic activity in adipose tissue results in an increased rate of fatty acid release into the plasma pool. Excess free fatty acids (FFAs) contribute to triglyceride (TG) secretion in the form of very-low-density lipoprotein (VLDL) and increase de novo lipogenesis in the liver [9]
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