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


CONCLUSIONS
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.
Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea.
Jung-Won
JW
Choi
Hao
H
Liu
Rajib
R
Mukherjee
Jong Won
JW
Yun
D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005227:Fatty Acids / Q000378:metabolism*; D060752:Fetuin-B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D050155:Lipogenesis; D008297:Male; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D029589:Seminal Plasma Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000090203:Zn-Alpha-2-Glycoprotein
D005227:Fatty Acids; D060752:Fetuin-B; D034741:RNA, Small Interfering; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein