Downregulation of Fetuin-B and Zinc-alpha 2-glycoprotein is Linked to Impaired Fatty Acid Metabolism in Liver Cells

作者：Choi Jung Won; Liu Hao; Mukherjee Rajib; Yun Jong Won^*

来源：Cellular Physiology and Biochemistry, 2012, 30(2): 295-306.

DOI：10.1159/000339065

• Plasma proteome
• High fat diet
• Obesity-prone and -resistant rats
• Fetuin-B
• Zinc-alpha 2-glycoprotein
• RNA interference

Background: Our recent proteomic study has shown that plasma protein levels of fetuin-B (Ft-B) and zinc-alpha 2-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.

• 出版日期2012