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.

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