Downregulation of fetuin-B and zinc-α2-glycoprotein is linked to impaired fatty acid metabolism in liver cells

Cell Physiol Biochem. 2012;30(2):295-306. doi: 10.1159/000339065. Epub 2012 Jun 22.

Abstract

Background: Our recent proteomic study has shown that plasma protein levels of fetuin-B (Ft-B) and zinc-α2-glycoprotein (ZAG) are significantly elevated in obesity-resistant (OR) rats exposed to a high fat diet. Time profiling of the plasma concentrations of Ft-B and ZAG in OR rats has shown stable regulation of these proteins throughout the entire period of rat breeding.

Methods: To firmly establish roles for these proteins in lipogenesis, we efficiently knocked down (KD) the genes FETUB and AZGP1 encoding Ft-B and ZAG, respectively, using siRNA in Chang liver cells.

Results: Reduced expression of FETUB and AZGP1 led to a significant increase in the expression of lipogenic genes, thereby resulting in higher lipid levels in both KD cells. Collectively with our previous findings, we confirmed that Ft-B was similarly regulated with Ft-A, in that their plasma protein levels were commonly reduced in diet-induced obese rats.

Conclusion: Our results provide a possible relationship between reduced plasma protein levels of Ft-B and ZAG and higher risk of diet-induced obesity through impaired fatty acid metabolism in hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diet, High-Fat
  • Down-Regulation*
  • Electrophoresis, Gel, Two-Dimensional
  • Fatty Acids / metabolism*
  • Fetuin-B / antagonists & inhibitors
  • Fetuin-B / genetics
  • Fetuin-B / metabolism*
  • Hepatocytes / metabolism*
  • Lipogenesis
  • Male
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Seminal Plasma Proteins / antagonists & inhibitors
  • Seminal Plasma Proteins / genetics
  • Seminal Plasma Proteins / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Zn-Alpha-2-Glycoprotein

Substances

  • Fatty Acids
  • Fetuin-B
  • RNA, Small Interfering
  • Seminal Plasma Proteins
  • Zn-Alpha-2-Glycoprotein