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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 \u03b1 (TNF\u03b1) 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.<\/jats:p>","DOI":"10.3390\/nu12092507","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T09:22:31Z","timestamp":1597828951000},"page":"2507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Wenyu","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanfen","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diangeng","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food 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Yangzhou 225004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwei","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China"},{"name":"(Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China"},{"name":"(Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China"},{"name":"Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China"},{"name":"Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1929-2202","authenticated-orcid":false,"given":"Zhennan","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2007-2143","authenticated-orcid":false,"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, 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