Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

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

International Journal of Obesity volume 33, pages 1023–1030 (2009)Cite this article

Abstract

Context:

Zinc-α2-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=−0.62, P<0.001), body mass index (r=−0.64, P<0.001), waist circumference(r=−0.68, P<0.001), hip circumference (r=−0.60, P<0.001), percentage of body fat (r=−0.52, P=0.03) and fat mass(r=−0.59, P=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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Ahima RS . Adipose tissue as an endocrine organ. Obesity (Silver Spring) 2006; 14 (Suppl 5): 242S–249S.

    Article  CAS  Google Scholar 

  2. Burgi W, Schmid K . Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma. J Biol Chem 1961; 236: 1066–1074.

    CAS  PubMed  Google Scholar 

  3. Poortmans JR, Schmid K . The level of Zn-alpha 2-glycoprotein in normal human body fluids and kidney extract. J Lab Clin Med 1968; 71: 807–811.

    CAS  PubMed  Google Scholar 

  4. Bondar OP, Barnidge DR, Klee EW, Davis BJ, Klee GG . LC-MS/MS quantification of Zn-alpha-2 glycoprotein: a potential serum biomarker for prostate cancer. Clin Chem 2007; 53: 673–678.

    Article  CAS  PubMed  Google Scholar 

  5. Stejskal D, Karpisek M, Reutova H, Stejskal P, Kotolova H, Kollar P . Determination of serum zinc-alpha-2-glycoprotein in patients with metabolic syndrome by a new ELISA. Clin Biochem 2008; 41: 313–316.

    Article  CAS  PubMed  Google Scholar 

  6. Hirai K, Hussey HJ, Barber MD, Price SA, Tisdale MJ . Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res 1998; 58: 2359–2365.

    CAS  PubMed  Google Scholar 

  7. Hale LP, Price DT, Sanchez LM, Demark-Wahnefried W, Madden JF . Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may serve as a potential serum marker for prostate cancer. Clin Cancer Res 2001; 7: 846–853.

    CAS  PubMed  Google Scholar 

  8. Russell ST, Zimmerman TP, Domin BA, Tisdale MJ . Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha-2-glycoprotein. Biochim Biophys Acta 2004; 1636: 59–68.

    Article  CAS  PubMed  Google Scholar 

  9. Bing C, Bao Y, Jenkins J, Sanders P, Manieri M, Cinti S et al. Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc Natl Acad Sci USA 2004; 101: 2500–2505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bao Y, Bing C, Hunter L, Jenkins JR, Wabitsch M, Trayhurn P . Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed and secreted by human (SGBS) adipocytes. FEBS Lett 2005; 579: 41–47.

    Article  CAS  PubMed  Google Scholar 

  11. Berndt J, Kovacs P, Ruschke K, Kloting N, Fasshauer M, Schon MR et al. Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes. Diabetologia 2007; 50: 1472–1480.

    Article  CAS  PubMed  Google Scholar 

  12. Diraison F, Dusserre E, Vidal H, Sothier M, Beylot M . Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity. Am J Physiol Endocrinol Metab 2002; 282: E46–E51.

    Article  CAS  PubMed  Google Scholar 

  13. Boizard M, Le Liepvre X, Lemarchand P, Foufelle F, Ferre P, Dugail I . Obesity-related overexpression of fatty-acid synthase gene in adipose tissue involves sterol regulatory element-binding protein transcription factors. J Biol Chem 1998; 273: 29164–29171.

    Article  CAS  PubMed  Google Scholar 

  14. Rolland V, Liepvre XL, Jump DB, Lavau M, Dugail I . A GC-rich region containing Sp1 and Sp1-like binding sites is a crucial regulatory motif for fatty acid synthase gene promoter activity in adipocytes. Implication In the overactivity of FAS promoter in obese Zucker rats. J Biol Chem 1996; 271: 21297–21302.

    Article  CAS  PubMed  Google Scholar 

  15. Chen HC, Stone SJ, Zhou P, Buhman KK, Farese Jr RV . Dissociation of obesity and impaired glucose disposal in mice overexpressing acyl coenzyme a:Diacylglycerol acyltransferase 1 in white adipose tissue. Diabetes 2002; 51: 3189–3195.

    Article  CAS  PubMed  Google Scholar 

  16. Sztalryd C, Komaromy MC, Kraemer FB . Overexpression of hormone-sensitive lipase prevents triglyceride accumulation in adipocytes. J Clin Invest 1995; 95: 2652–2661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jocken JW, Langin D, Smit E, Saris WH, Valle C, Hul GB et al. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab 2007; 92: 2292–2299.

    Article  CAS  PubMed  Google Scholar 

  18. Carlsson E, Johansson LE, Strom K, Hoffstedt J, Groop L, Holm C et al. The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects. Int J Obes (Lond) 2006; 30: 1442–1448.

    Article  CAS  Google Scholar 

  19. Gong FY, Shi YF, Deng JY . The regulatory mechanism by which interleukin-6 stimulates GH-gene expression in rat GH3 cells. J Endocrinol 2006; 190: 397–406.

    Article  CAS  PubMed  Google Scholar 

  20. Gong FY, Deng JY, Shi YF . IFN-gamma increases the hGH gene promoter activity in rat GH3 cells. Horm Res 2003; 60: 14–20.

    CAS  PubMed  Google Scholar 

  21. Gong FY, Deng JY, Shi YF . Stimulatory effect of interleukin-1beta on growth hormone gene expression and growth hormone release from rat GH3 cells. Neuroendocrinology 2005; 81: 217–228.

    Article  CAS  PubMed  Google Scholar 

  22. Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402–408.

    Article  CAS  PubMed  Google Scholar 

  23. Todorov PT, McDevitt TM, Meyer DJ, Ueyama H, Ohkubo I, Tisdale MJ . Purification and characterization of a tumor lipid-mobilizing factor. Cancer Res 1998; 58: 2353–2358.

    CAS  PubMed  Google Scholar 

  24. Kamoshida S, Watanabe K, Suzuki M, Mizutani Y, Sakamoto K, Sugimoto Y et al. Expression of cancer cachexia-related factors in human cancer xenografts: An immunohistochemical analysis. Biomed Res 2006; 27: 275–281.

    Article  CAS  PubMed  Google Scholar 

  25. Groundwater P, Beck SA, Barton C, Adamson C, Ferrier IN, Tisdale MJ . Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients. Br J Cancer 1990; 62: 816–821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Marrades MP, Martinez JA, Moreno-Aliaga MJ . ZAG, a lipid mobilizing adipokine, is downregulated in human obesity. J Physiol Biochem 2008; 64: 61–66.

    Article  CAS  PubMed  Google Scholar 

  27. Dahlman I, Kaaman M, Olsson T, Tan GD, Bickerton AS, Wahlen K et al. A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects. J Clin Endocrinol Metab 2005; 90: 5834–5840.

    Article  CAS  PubMed  Google Scholar 

  28. Rolli V, Radosavljevic M, Astier V, Macquin C, Castan-Laurell I, Visentin V et al. Lipolysis is altered in MHC class I zinc-alpha(2)-glycoprotein deficient mice. FEBS Lett 2007; 581: 394–400.

    Article  CAS  PubMed  Google Scholar 

  29. Russell ST, Tisdale MJ . Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo. Br J Cancer 2002; 87: 580–584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by the national natural science foundation of China (No.: 30540036 and 30771026)

Author information

Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    F-Y Gong, J-Y Deng, H-J Zhu, H Pan, N-S Li & Y-F Shi

  2. Department of Endocrinology, the People's Hospital of Shanxi Provine, Taiyuan, Shanxi, China

    S-J Zhang

Authors
  1. F-Y Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S-J Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J-Y Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H-J Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N-S Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y-F Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F-Y Gong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gong, FY., Zhang, SJ., Deng, JY. et al. Zinc-α2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue. Int J Obes 33, 1023–1030 (2009). https://doi.org/10.1038/ijo.2009.141

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2009.141

Keywords

This article is cited by

Search

Advanced search

Quick links