Activated AMPK explains hypolipidemic effects of sulfated low molecular weight guluronate on HepG2 cells

Xin Liu; Jie-Jie Hao; Li-Juan Zhang; Xia Zhao; Xiao-Xi He; Miao-Miao Li; Xiao-Liang Zhao; Jian-Dong Wu; Pei-Ju Qiu; Guang-Li Yu

doi:10.1016/j.ejmech.2014.07.107

Activated AMPK explains hypolipidemic effects of sulfated low molecular weight guluronate on HepG2 cells

Eur J Med Chem. 2014 Oct 6:85:304-10. doi: 10.1016/j.ejmech.2014.07.107. Epub 2014 Jul 30.

Authors

Affiliations

¹ 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.
² 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: [email protected].

PMID: 25089813
DOI: 10.1016/j.ejmech.2014.07.107

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).

Keywords: AMPK; HepG2; Hypolipidemia; SREBP; Sulfated low molecular weight guluronate (SLMG).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism*
Acetyl-CoA Carboxylase / metabolism
Cell Proliferation / drug effects
Cholesterol / metabolism
Cholesterol 7-alpha-Hydroxylase / metabolism
Down-Regulation / drug effects
Enzyme Activation / drug effects
Fatty Acids / metabolism
Hep G2 Cells
Hexuronic Acids / chemistry*
Hexuronic Acids / pharmacology*
Humans
Hydroxymethylglutaryl CoA Reductases / metabolism
Hypolipidemic Agents / chemistry*
Hypolipidemic Agents / pharmacology*
Molecular Weight
Oxidation-Reduction / drug effects
Phosphorylation / drug effects
Receptors, LDL / metabolism
Sterol Regulatory Element Binding Protein 1 / metabolism
Sterol Regulatory Element Binding Protein 2 / metabolism
Sulfates / chemistry*
Triglycerides / metabolism

Substances

Fatty Acids
Hexuronic Acids
Hypolipidemic Agents
LDLR protein, human
Receptors, LDL
SREBF1 protein, human
SREBF2 protein, human
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Sulfates
Triglycerides
guluronic acid
Cholesterol
Hydroxymethylglutaryl CoA Reductases
CYP7A1 protein, human
Cholesterol 7-alpha-Hydroxylase
AMP-Activated Protein Kinases
Acetyl-CoA Carboxylase