Effects of Zinc Alpha2 Glycoprotein on Lipid Metabolism of Liver in High-Fat Diet-Induced Obese Mice

Abstract

Zinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.

Metabolomic and microarray analyses of adipose tissue of dapagliflozin-treated mice, and effects of 3-hydroxybutyrate on induction of adiponectin in adipocytes

“…S4b ). Zinc alpha 2-glycoprotein (Azgp1) is a lipid mobilizing factor 24 , and its expressions were significantly higher in KKAy + Dapa than KK or KKAy (Supplementary Fig. S4c ).…”

“…The second is the effect of lipid mobilizing factor, Azgp1 (zinc alpha 2-glycoprotein). Injection of Azgp1 expression plasmid reduces hepatic TG content and expressions of lipogenic genes 24 . In the current study, expressions of Azgp1 were significantly elevated in liver of KKAy + Dapa compared with KKAy.…”

Zinc-α2-Glycoprotein Is Associated with Obesity in Chinese People and HFD-Induced Obese Mice

“…Regarding the issue of endogenous vs. exogenous ZAG, our previous studies together with others showed that injection of a ZAG expression plasmid in mice could increase serum ZAG levels (Gong et al, 2009 ; Fan et al, 2017 ) as well as Zag gene expression in eVAT (Gong et al, 2009 ). In our present study, we found that administration of a ZAG expression plasmid to mice led to an increase in Zag expression in pVAT (Figure 5A ) as well as a tendency toward an increase in sWAT (Figure 4B ).…”

Zinc supplementation reduces diet-induced obesity and improves insulin sensitivity in rats

“…Thus, dysfunction of zinc signaling may be involved in the pathogenesis of diabetes mellitus (Nicolson et al 2009). On the other hand, zinc supplementation protected against apoptosis and reduced liver damage in patients with chronic hepatitis C or compensated cirrhosis (Fan et al 2017;Matsuoka et al 2009;Sun et al 2015).…”

“…These are essential amino acids, which participate in the regulation of body protein balance and insulin secretion, modulation of the immune system, and reduction of muscle injury post-exercise (Fan et al 2017;Holecek 2018). Elevated blood levels of BCAA are found in obesity and type 2 diabetes mellitus (Batch et al 2014;Newgard et al 2009), making them putative biomarkers of these metabolic diseases (Siomkajlo et al 2017).…”