title: Luteolin improves non-alcoholic fatty liver disease in db/db mice by inhibition of liver X receptor activation to down-regulate expression of sterol regulatory element binding protein 1c.
abstract: In this study, we report that daily administration of luteolin for 8 weeks improved hepatic steatosis by repressing hepatic TG accumulation and increasing glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the livers of db/db mice. Further in vitro studies revealed that luteolin can competitively bind to the ligand binding domain to suppress the LXR activation induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in HepG2 cells and primary hepatocytes. Taken together, our results indicate that luteolin can abolish lipid accumulation induced by LXR-SREBP-1c activation both in vivo and in vitro, and may have potential as a therapeutic agent for treating NAFLD.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lin
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, Jiangsu, China. Electronic address: zhuyx@njmu.edu.cn.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Jingling Hospital, School of Medicine, Nanjing University, China. Electronic address: lijiemd@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005227:Fatty Acids / Q000737:chemistry; D005951:Glucose Tolerance Test; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D000071518:Liver X Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D047311:Luteolin
keywords: Fatty acid; Liver X receptor; Luteolin; Non-alcoholic fatty liver disease; db/db mouse