Effect of Zn-α2-glycoprotein on liver gene expression in obese mice by gene expression profiling

Abstract

Objectives To explore the effect of Zn-α2-glycoprotein(ZAG) on hepatic gene expression profiles in obese mice by using microarray technology. Methods The model of obese ICR mice induced by high fat diet (HFD) was established, and then the 21 mice models were divided into ZAG-treating group (ZAG group,n=8) and HFD group (n=13). Another 10 ICR mice were set as blank control (fed with standard food, SF group). Then the ZAG group were treated with ZAG expression plasmid injection and high fat diet; the HFD group were treated with negative saline injection and high fat diet; the SF group were treated with negative saline injection and standard food. Eight weeks later, the biochemical indexes of each group, such as the levels of blood glucose, blood lipids, fasting insulin and so on were checked. The gene expression profiles in liver, especially genes related to the glucolipid metabolism, were examined by the GeneChip microarray system, and the expression of glycogen synthase 2 (GYS2), peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1α) and suppressor of cytokine signaling 3 (SOCS3) were verified by quantitative real time polymerase chain reaction (qRT-PCR). The t test was used when data were compared between two groups. Results After 8-week of intervention, the body weight, white adipose tissue mass and fasting glucose level in ZAG group decreased by 14.5%, 57.17% and 35.5% respectively when compared with those in HFD group(F=7.948, 18.941, 4.327, all P<0.05). A total of 424 genes (299 increased, 125 decreased) expressed differentially in the two groups. Among them, six genes (enoyl-coenzyme A(Ehhadh), 3-ketoacyl-CoA thiolase 1(ACAA1), long-chain fatty-acid-coenzyme A ligase 1 (ACSL1), glucose-6-phosphate(G6P), PGC-1α and SOCS3) were found to be involved with glucose and lipid metabolism. Compared with those in the HFD group, the expression of PGC-1α and SOCS3 increased by 1.97 and 4.15 folds, while the expression of Ehhadh, ACAA1, ACSL1, G6P reduced to 0.35, 0.58, 0.52 and 0.33 folds, respectively. Quantitative real time PCR was used to confirm the results of partial genes, which was in accordance with the result of cDNA microarray analysis. Conclusions ZAG may significant improve the glucolipid metabolism in the obese mice. The beneficial action of ZAG may be associated with down-regulation of ACSL1 and G6P, up-regulation of PGC-1α and GYS2 expression in liver. Key words: Gene chip; Glucolipid metabolism; Zinc-α2-glycoprotein; acyl-CoA synthetase long-chain family member 1; Peroxisome proliferator-activated receptor gamma coactivator 1 alpha