SOVREMENNAYA PEDIATRIYA.2016.3(75):132-136; doi10.15574/SP.2016.75.132 

The expression of NAMPT, PLOD2, FBN1, and IFRD genes in blood cells in the obese adolescents with insulin resistance 

Minchenko D. O., Tiazhka O. V., Hnatiuk O. S., Minchenko O. H.

National O.O. Bohomolets Medical University, Kyiv, Ukraine

Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kyiv, Ukraine 

Objective. To study the expression of genes encoded enzymes NAMPT and PLOD2 as well as protein of extracellular matrix FBN1 interferon-related developmental regulator IFRD in blood cells of obese adolescents with normal and impaired insulin sensitivity.

Materials and Methods. For this study were used three groups of adolescent boys with mean age 14 years: normal without obesity indication (control) and obese individuals with normal and impaired insulin sensitivity. RNA was extracted from blood cells and the levels of gene expressions were studied using quantitative real-time polymerase chain reaction.

Results. It was shown that the expression level of NAMPT and IFRD genes is decreased, but PLOD2 and FBN1 genes — is increased in the blood cells of obese adolescent boys with normal insulin sensitivity as compared to control group. Development of insulin resistance in obese adolescents leads to suppression of PLOD2 and FBN1 genes expression level and additional down-regulation of NAMPT gene expression in the blood cells as compared to obese adolescent

boys with normal insulin sensitivity. At the same time, no significant changes were found in the expression level of IFRD gene in the blood cells of obese adolescents with insulin resistance as compared to obese group with normal insulin sensitivity.

Conclusions. We shown that the expression level of polyfunctional enzymes NAMPT and PLOD2 as well as protein of extracellular matrix FBN1 and interferon-related developmental regulator IFRD, which participate in the regulation of metabolic processes, are significantly deregulated in blood cells in obese adolescents with normal and suppressed insulin sensitivity and that insulin resistance in obesity is associated with changes in the expression level of three studied genes (NAMPT, PLOD2 and FBN1), which possibly can contribute to the development of insulin resistance.

Key words: obesity, adolescents, insulin resistance, gene expressions, NAMPT, PLOD2, FBN1, IFRD, blood cells.

REFERENCES

1. Tiazhka OV, Minchenko DO, Davydov VV, Moliavko OS et al. 2014. Expression of genes, which control glucose metabolism, in the blood of the obese boys with insulin resistance. Sovremennaya pediatriya. 6(62): 112—115.

2. Minchenko DO. 2015. Molecular bases of the development of obesity and its metabolic complications in children. Sovremennaya pediatriya. 2(66): 109—112.

3. Minchenko DO, Hnatiuk OS, Tiazhka OV, Minchenko OH. 2015. Development of insulin resistance in the obese adolescents changes the expression level of CLU, PCOLCE, COL5A1 and TYMP genes in blood cells . Sovremennaya pediatriya. 7(71): 127—130.

4. Maslak HS, Kostiuk O, Minchenko DO ta in. 2014. Sialovanist hlikoproteiniv plazmatychnoi membrany limfotsytiv liudyny i ekspresiia NEU1 ta ST6GAL1 mRNK za erytremii. Fiziol zhurn. 60; 5: 14—22.

5. Yamaoka M, Maeda N, Nakamura S et al. 2012. A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells. PLoS One. 7; 10: 47377.

6. Yamaoka M, Maeda N, Takayama Y et al. 2014. Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat. PLoS One. 9; 11: 112813.

7. Bravo RL, Parra V, Gatica D et al. 2013. Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration. Int Rev Cell Mol Biol. 301: 215—290. http://dx.doi.org/10.1016/B978-0-12-407704-1.00005-1; PMid:23317820 PMCid:PMC3666557

8. Han J, Kaufman RJ. 2014. Measurement of the unfolded protein response to investigate its role in adipogenesis and obesity. Methods Enzymol. 538: 135—150. http://dx.doi.org/10.1016/B978-0-12-800280-3.00008-6; PMid:24529437

9. Gilkes DM, Bajpai S, Chaturvedi P et al. 2013. Hypoxia-inducible factor 1 (HIF-1) promotes extracellular matrix remodeling under hypoxic conditions by inducing P4HA1, P4HA2, and PLOD2 expression in fibroblasts. J Biol Chem. 288; 15: 10819—10829. http://dx.doi.org/10.1074/jbc.M112.442939; PMid:23423382 PMCid:PMC3624462

10. Ando H, Kumazaki M, Motosugi Y, Ushijima K et al. 2011. Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice. Endocrinology. 152; 4: 1347—1354. http://dx.doi.org/10.1210/en.2010-1068; PMid:21285316

11. Bochkov VN, Philippova M, Oskolkova O et al. 2006. Oxidized phospholipids stimulate angiogenesis via induction of VEGF, IL-8, COX-2 and ADAMTS-1 metalloprotease, implicating a novel role for lipid oxidation in progression and destabilization of atherosclerotic lesions. Circ Res 99; 8: 900—908. http://dx.doi.org/10.1161/01.RES.0000245485.04489.ee; PMid:16973904

12. Stastny J, Bienertova-Vasku J, Vasku A. 2012. Visfatin and its role in obesity development. Diabetes Metab Syndr. 6; 2: 120—124. http://dx.doi.org/10.1016/j.dsx.2012.08.011; PMid:23153983

13. Zhao C, Datta S, Mandal P et al. 2010. Stress-sensitive regulation of IFRD1 mRNA decay is mediated by an upstream open reading frame. J Biol Chem. 285; 12: 8552—8562. http://dx.doi.org/10.1074/jbc.M109.070920; PMid:20080976 PMCid:PMC2838277

14. Minchenko D, Ratushna O, Bashta Y et al. 2013. The expression of TIMP1, TIMP2, VCAN, SPARC, CLEC3B and E2F1 in subcutaneous adipose tissue of obese males and glucose intolerance. Cell Bio. 2; 2: 25—33. http://dx.doi.org/10.4236/cellbio.2013.22006

15. Chang YC, Chang TJ, Lee WJ, Chuang LM. 2010. The relationship of visfatin/pre-B-cell colony-enhancing factor/nicotinamide phosphoribosyltransferase in adipose tissue with inflammation, insulin resistance, and plasma lipids. Metab Clin Exp. 59; 1: 93—99. http://dx.doi.org/10.1016/j.metabol.2009.07.011; PMid:19765775