Zinc-α2-Glycoprotein Knockout Influenced Genes Expression Profile in Adipose Tissue and Decreased the Lipid Mobilizing After Dexamethasone Treatment in Mice

Abstract

Zinc-α2-glycoprotein (ZAG), as an adipokine, plays an important role in lipid metabolism. However, its influence on whole gene expression profile in adipose tissue is not known. Under stress condition, how ZAG affects the lipid metabolism is also unclear. Therefore, in this study ZAG systemic knockout (KO) mice were used as a model to reveal the genes expression profile in visceral fat tissues of ZAG KO mice and wild-type mice by genome-wide microarray screening. Then dexamethasone (DEX) was used to explore the effect of ZAG deletion on body fat metabolism under stress. Our results showed that 179 genes were differentially expressed more than 1.5 times between ZAG KO mice and wild type mice, of which 26 genes were upregulated dramatically and 153 genes were significantly downregulated. Under DEX simulated stress, ZAG systemic knockout in vivo resulted in a markedly decrease of triglycerides (TG) and nonesterified fatty acid (NEFA) content in in plasma. Similarly, for lipid catabolism, ZAG KO led to a significant increase of phosphorylated HSL (p-HSL) protein and a rising tendency of adipose triglyceride lipase (ATGL) protein relative to those of the DEX group. For lipid anabolism, fatty acid synthase (FAS) and adiponectin protein expression in visceral fat rose notably in ZAG KO mice after DEX treatment. In conclusion, ZAG knockout can affect the gene expression profile of adipose tissue, reduce elevated TG and NEFA levels in plasma, and alter lipid metabolism under DEX treatment. These findings provide new insights into the mechanism of lipid metabolic disorders in response to stress.

Adipose and serum zinc alpha-2-glycoprotein (ZAG) expressions predict longitudinal change of adiposity, wasting and predict survival in dialysis patients

“…We also reduced the confounding effects of such by adding metabolic and nutritional parameters such as albumin, lipids profile and BMI into the statistical analysis model. Furthermore, ZAG levels are also altered in acute stress conditions like sepsis and critical illnesses 46 – 48 , though we attempted to reduce the bias through exclusion of patients who were critically ill and unfit for peritoneal dialysis catheter insertion. Lastly, we did not evaluate other associated up- and down-stream biomarkers, therefore we are unable to infer the overall pathogenic pathway and establish the pathophysiological mechanisms with the clinical outcomes we studied.…”