title: Activated AMPK explains hypolipidemic effects of sulfated low molecular weight guluronate on HepG2 cells.
abstract: Low molecular weight and sulfated low molecular weight guluronate (LMG and SLMG) were prepared and hypolipidemic effects were studied in a human hepatocellular carcinoma HepG2 cell line. Both compounds decreased total cholesterol (TC) and triglycerides (TG) and inhibited 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity in HepG2 cells. In general, SLMG had greater effects than LMG. Activation of sterol regulatory element-binding protein 2 (SREBP-2), low density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK), and AMPK's downstream targets were evidenced by increased phosphorylation of AMPK, HMGCR, and acetyl-CoA-carboxylase (ACC), which decreased HMGRC and ACC activity. We further demonstrated that activated AMPK was linked to down-regulated SREBP-1 and up-regulated cholesterol 7α-hydroxylase (CYP7A1).
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Jie-Jie
authors.initials: JJ
authors.lastname: Hao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: He
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Li
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Wu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Pei-Ju
authors.initials: PJ
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. Electronic address: glyu@ouc.edu.cn.
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Yu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D056945:Hep G2 Cells; D006603:Hexuronic Acids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000494:pharmacology*; D008970:Molecular Weight; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011973:Receptors, LDL / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D013431:Sulfates / Q000737:chemistry*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D006603:Hexuronic Acids; D000960:Hypolipidemic Agents; C573412:LDLR protein, human; D011973:Receptors, LDL; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D013431:Sulfates; D014280:Triglycerides; C007896:guluronic acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase
keywords: AMPK; HepG2; Hypolipidemia; SREBP; Sulfated low molecular weight guluronate (SLMG)