Journal of Physiology and Biochemistry

, Volume 64, Issue 1, pp 61–66 | Cite as

ZAG, a lipid mobilizing adipokine, is downregulated in human obesity

  • M. P. Marrades
  • J. A. Martínez
  • M. J. Moreno-Aliaga
Article

Abstract

The main goal of this study was to compare the expression of Zinc-α2-glycoprotein (ZAG), a recently described adipokine, in obese and lean subjects. ZAG expression was determined by Real-time PCR analysis in subcutaneous abdominal adipose tissue of eighteen young men, 9 lean (BMI=23.1±0.4 kg/m2) and 9 obese (34.7±1.2 kg/m2) with a similar habitual dietary intake of fat and physical activity, which were assessed by validated methods. Our data revealed that ZAG gene was downregulated (−70%; p<0.05) in subcutaneous adipose tissue of obese compared to lean subjects. Moreover, statistically significant positive correlations between ZAG gene expression and serum adiponectin (r=0.89; p<0.01) and a negative correlation with the plasma levels of leptin (r=−0.82; p<0.05) and waist circumference (r=−0.64; p<0.05) were found in obese subjects. Our data suggest that this novel adipokine could play a role in human susceptibility to obesity related disorders and that upregulation of ZAG could be a promising therapeutic target for metabolic syndrome treatment.

Key words

Adipose tissue Diet induced obesity ZAG 

La expresión génica de ZAG, una adipoquina lipolítica, está reprimida en sujetos obesos

Resumen

El objetivo del presente estudio fue la comparación de los niveles de expresión génica de ZAG (Zinc-α2-gylcoprotein), una adipoquina lipolítica, entre sujetos obesos y normoponderales. Los niveles de expresión del gen ZAG se determinaron mediante PCR en tiempo real en tejido adiposo subcutáneo de 18 adultos jóvenes, 9 de ellos normoponderales (IMC=23,1±0,4 kg/m2) y 9 obesos (IMC=34,7±1,2 kg/m2), que presentaban una ingesta calórica similar y una actividad física moderada. Los niveles de expresión de ZAG estaban reprimidos (−70%; p<0,05) en el tejido adiposo subcutáneo de los sujetos obesos en comparación con los normoponderales. Además, los niveles de ZAG se correlacionaron positivamente con los niveles plasmáticos de adiponectina (r=0,89; p<0,01) y negativamente con los niveles de leptina (r=−0,82; p<0,05) y el perímetro de la cintura (r=∮0,64; p<0,05) en los sujetos obesos. Estos datos sugieren que la menor expresión de esta nueva adipoquina podría explicar la mayor acumulación de triglicéridos en los adipocitos de los sujetos obesos, y contribuir a la susceptibilidad a desarrollar desórdenes relacionados con la obesidad.

Palabras clave

Tejido adiposo Obesidad inducida por la dieta ZAG 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bao, Y., Bing, C., Hunter, L., Jenkins, J.R., Wabitsch, M. and Trayhurn, P. (2005): Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed and secreted by human (SGBS) adipocytes. FEBS Lett, 579, 41–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Bing, C., Bao, Y., Jenkins, J., Sanders, P., Manieri, M., Cinti, S., Tisdale, M.J. and Trayhurn, P. (2004): Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is upregulated in mice with cancer cachexia. Proc Natl Acad Sci USA, 101, 2500–2505.PubMedCrossRefGoogle Scholar
  3. 3.
    Gohda, T., Makita, Y., Shike, T., Tanimoto, M., Funabiki, K., Horikoshi, S. and Tomino, Y. (2003): Identification of epistatic interaction involved in obesity using the KK/Ta mouse as a Type 2 diabetes model: is Zn-alpha2 glycoprotein-1 a candidate gene for obesity?Diabetes, 52, 2175–2181.PubMedCrossRefGoogle Scholar
  4. 4.
    Havel, P.J. (2004): Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes, 53, S143–151.CrossRefGoogle Scholar
  5. 5.
    Hirai, K., Hussey, H.J., Barber, M.D., Price, S.A. and Tisdale, M.J. (1998): Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res, 58, 2359–2365.PubMedGoogle Scholar
  6. 6.
    Kettaneh, A., Heude, B., Romon, M., Oppert, J.M., Borys, J.M., Balkau, B., Ducimetiere, P. and Charles, M.A. (2007): High plasma leptin predicts an increase in subcutaneous adiposity in children and adults. Eur J Clin Nutr, 61, 719–26.PubMedCrossRefGoogle Scholar
  7. 7.
    Lemieux, I., Lamarche, B., Couillard, C., Pascot, A., Cantin, B., Bergeron, J., Dagenais, G. R. and Despres, J.P. (2001): Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch Intern Med, 161, 2685–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Marrades, M.P., Martínez, J.A. and Moreno-Aliaga, M.J. (2007): Differences in short-term metabolic responses to a lipid load in lean (resistant) vs obese (susceptible) young male subjects with habitual high-fat consumption. Eur J Clin Nutr, 61, 166–74.PubMedCrossRefGoogle Scholar
  9. 9.
    Marrades, M.P., Milagro, F.I., Martínez, J.A. and Moreno-Aliaga, M.J. (2006): Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers. Biochem Biophys Res Commun, 339, 785–789.PubMedCrossRefGoogle Scholar
  10. 10.
    Matsuzawa, Y., Funahashi, T., Kihara, S. and Shimomura, I. (2004): Adiponectin and metabolic syndrome. Arterioscler. Thromb. Vasc. Biol., 24, 29–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Murray, I., Sniderman, A.D., Havel, P.J. and Cianflone, K. (1999): Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. J Biol Chem, 274, 36219–36225.PubMedCrossRefGoogle Scholar
  12. 12.
    Rolli, V., Radosavljevic, M., Astier, V., Macquin, C., Castan-Laurell, I., Visentin, V., Guigné, C., Carpéné, C., Valet, P., Gilfillan, S. and Bahram, S. (2007): Lipolysis is altered in MHC class I zinc-alpha(2)-glycoprotein deficient mice. FEBS Lett, 581, 394–400.PubMedCrossRefGoogle Scholar
  13. 13.
    Russell, S.T., Zimmerman, P., Domin, A.B. and Tisdale, M.J. (2004): Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha2-glycoprotein. Biochim Biophys Acta, 1636, 59–68.PubMedGoogle Scholar
  14. 14.
    Santos, J.L., Boutin, P., Verdich, C., Claus, H., Larsen, L.H., Toubro, S., Dina, C., Saris, W.H., Blaak, E.E., Hoffstedt, J., Taylor, M.A., Polak, J., Clement, K., Langin, D., Astrup, A., Froguel, P., Pedersen, O., Sorensen, T. I. A., Martínez, J. A. and Nugenob C. (2006): Genotype-by-nutrient interactions assessed in European obese women. A case-only study. Eur J Nut, 45, 454–462.CrossRefGoogle Scholar

Copyright information

© Universidad de Navarra 2008

Authors and Affiliations

  • M. P. Marrades
    • 1
  • J. A. Martínez
    • 1
  • M. J. Moreno-Aliaga
    • 1
  1. 1.Department of Nutrition and Food Science, Physiology and ToxicologyUniversity of NavarraPamplonaSpain

Personalised recommendations