Zinc-α2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue

Abstract

Context: Zinc-a2-glycoprotein (ZAG) was found to influence lipolysis in adipose tissue and has recently been proposed as a candidate factor in the regulation of body weight. Objective: To elucidate the association of serum ZAG level with body weight and percentage of body fat in normal, obese subjects and high-fat diet (HFD)-induced obese mice. Design: The relationship between serum ZAG and obesity-related parameters was studied in 44 human subjects and 36 mice fed standard food and HFD. Furthermore, the effects of ZAG overexpression on adipose tissue of mice was also evaluated by using a liposome transfection method. Results: Serum ZAG level was significantly lower in obese patients and obese mice in comparison to that in people and mice with normal weight. The further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r ¼ À0.62, Po0.001), body mass index (r ¼ À0.64, Po0.001), waist circumference(r ¼ À0.68, Po0.001), hip circumference (r ¼ À0.60, Po0.001), percentage of body fat (r ¼ À0.52, P ¼ 0.03) and fat mass(r ¼ À0.59, P ¼ 0.01) in human subjects after adjustment for age and sex. Furthermore, ZAG overexpression in mice reduced body weight and the percentage of epididymal fat. The decreased FAS, ACC1 and DGAT mRNA and the increased HSL mRNA were also observed in epididymal adipose tissue in ZAG overexpression mice. Conclusion: ZAG is closely linked to obesity. Serum ZAG level is inversely associated with body weight and percentage of body fat. The action of ZAG is associated with downregulated lipogenic enzymes and upregulated lipolytic enzyme expressions in adipose tissue of mice.

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

“…60 In contrast, ZAG-overexpressing transgenic mice exhibited decreased body weight and epididymal fat, which was accompanied by a reduction in mRNA levels of fatty acid synthase, acetyl-CoA carboxylase-1 and acyl-coenzyme A: diacylglycerol transferase and the increase in mRNA levels of hormone-sensitive lipase in epididymal adipose tissue. 52 The potential role of ZAG in cholesterol metabolism has also been implicated by a recent study, in which a polymorphism in the ZAG gene is found to be associated with total cholesterol and low-density lipoprotein cholesterol in human subjects. 61 In addition to lipid metabolism, ZAG may be involved in the regulation of adiposity through modulating the production of other adipokines.…”

“…51 Similar to the findings in genetic models of obesity, a decrease in adipose tissue ZAG mRNA and serum ZAG levels has been reported in mice, in which obesity is induced by a high-fat diet. 52 In human subjects, using a gene profiling approach ZAG transcripts have been reported to be decreased in subcutaneous fat of obese women. 53 ZAG gene and protein expression has also been shown to be downregulated in subcutaneous and visceral adipose tissue of obese men and women in comparison with lean controls.…”

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

“…Serum ZAG levels have been found to be significantly lower in mice fed a high fat diet than those fed a normal diet (7), as well as in obese humans and mice (8). While ZAG overexpression in mice reduced both the body weight and weight of epididymal fat (8), ZAG knockout animals showed an increased body weight, especially when fed a high fat diet (9). These results suggest that ZAG, like leptin, is closely associated with fat mass.…”

“…Treatment of ob/ob mice with ZAG decreased body weight and fat mass and improved the parameters of insulin resistance including decreasing plasma levels of glucose, insulin and non-esterified fatty acids (NEFA), improving insulin sensitivity, and increasing muscle mass (6). Serum ZAG levels have been found to be significantly lower in mice fed a high fat diet than those fed a normal diet (7), as well as in obese humans and mice (8). While ZAG overexpression in mice reduced both the body weight and weight of epididymal fat (8), ZAG knockout animals showed an increased body weight, especially when fed a high fat diet (9).…”

Hydroxysafflor yellow A (HYSA) inhibited the proliferation and differentiation of 3T3-L1 preadipocytes

“…Quantitative real-time RT-PCR (qRT-PCR) was performed with SYBR green fluorescent dye using an ABI7500 PCR system (Applied Biosystems, Foster City, CA, USA) as previously described (Gong et al 2009). In brief, 3T3-L1 preadipocytes were plated in 24-well plate with a density of 2 9 10 4 /ml, then differentiated and treated with HSYA as above.…”