• The expression of DDX58, IFIH1, IFI16, and AIM2 genes in obese adolescents and men with insulin resistance

The expression of DDX58, IFIH1, IFI16, and AIM2 genes in obese adolescents and men with insulin resistance

SOVREMENNAYA PEDIATRIYA.2017.7(87):106-111; doi 10.15574/SP.2017.87.106

Minchenko D. O.
Bohomolets National Medical University, Kyiv, Ukraine
Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kyiv, Ukraine

Objective. To study the expression of genes encoded DDX58, IFIH1, IFI16 and AIM2 protein in lymphocytes of adolescents and adipose tissue of men in obesity associated with normal and impaired insulin sensitivity. Materials and methods. For this study adolescents and adult men were divided into three groups: normal without obesity (control) and obese individuals with normal and impaired insulin sensitivity. RNA was extracted from lymphocytes and adipose tissue and the levels of DDX58, IFIH1, IFI16, AIM2 and LEP gene expression were studied using quantitative real-time polymerase chain reaction.
Results. It was shown that the expression level of DDX58, IFIH1, IFI16 and AIM2 genes was significantly increased in lymphocytes of obese adolescents with normal and impaired insulin sensitivity as compared to control group, but insulin resistance was associated to a lesser extent with change of DDX58 gene expression and to a greater extent with change of other genes. At the same time, in adipose tissue of obese men the less noticeable changes in the induction of DDX58 and IFI16 genes were founded, but as for IFIH1 and AIM2 genes, their expression, on contrary, decreased. The level of LEP gene expression significantly increased in adipose tissue of obese men with normal and impaired 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. It was shown that the expression level of DDX58, IFIH1, IFI16 and AIM2 polyfunctional proteins, which participate in the metabolic regulation and immune response, is significantly disordered in blood cells in obese adolescents with normal and impaired insulin sensitivity and that insulin resistance in obesity is associated with significantly less changes in the expression level of DDX58 gene and to a greater extent of other genes. The observed changes in the expression of DDX58 and IFI16 genes partly reflect the changes of these gene expressions in adipose tissue.
Keywords: obesity, insulin resistance, adolescents, men, gene expressions, DDX58, IFIH1, IFI16, lymphocytes, adipose tissue.


1. Тяжка О.В., Мінченко Д.О., Молявко О.С. et al. (2014). Експресія генів ALDOC, TIGAR, ENO1 та ENO2 у крові дітей чоловічої статі з ожирінням, ускладненим резистентністю до інсуліну. 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. doi 10.15574/SP.2015.65.10

3. Маслак Г.С., Костюк О., Мінченко Д.О. et al. (2014). Сіальованість глікопротеїнів плазматичної мембрани лімфоцитів людини і експресія NEU1 та ST6GAL1 мРНК за еритремії. Фізіол. журн. 60; 5: 14—22.

4. 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: e47377.

5. 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: e112813.

6. Bravo R, 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. https://doi.org/10.1016/B978-0-12-407704-1.00005-1
PMid:23317820 PMCid:PMC3666557

7. Han J, Kaufman RJ. (2014). Measurement of the unfolded protein response to investigate its role in adipogenesis and obesity. Methods Enzymol. 538: 135—150. https://doi.org/10.1016/B978-0-12-800280-3.00008-6

8. Ando H, Kumazaki M, Motosugi Y et al. (2011). Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice. Endocrinology. 152; 4: 1347—1354. https://doi.org/10.1210/en.2010-1068

9. Lencer WI, DeLuca H, Grey MJ, Cho JA. (2015). Innate immunity at mucosal surfaces: the IRE1-RIDD-RIG-I pathway. Trends Immunol. 36; 7: 401—409. https://doi.org/10.1016/j.it.2015.05.006
PMid:26093676 PMCid:PMC4490948

10. Dutta D, Ghosh S, Pandit K et al. (2012). Leptin and cancer: Pathogenesis and modulation. Indian J Endocrinol Metab. 6; Suppl 3: 596—600. https://doi.org/10.1038/bjc.2011.584
PMid:22240784 PMCid:PMC3322960

11. Cui J, Chen Y, Wang HY, Wang RF. (2014). Mechanisms and pathways of innate immune activation and regulation in health and cancer. Hum Vaccin Immunother. 10; 11: 3270—3285. https://doi.org/10.4161/21645515.2014.979640
PMid:25625930 PMCid:PMC4514086

12. 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. https://doi.org/10.1161/01.RES.0000245485.04489.ee

13. Tsuchihara K, Ogura T, Fujioka R et al. (2008). Susceptibility of Snark-deficient mice to azoxymethane-induced colorectal tumorigenesis and the formation of aberrant crypt foci. Cancer Sci. 99; 4: 677—682. https://doi.org/10.1111/j.1349-7006.2008.00734.x

14. Gray EE, Winship D, Snyder JM et al. (2016). The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA. Immunity. 45; 2: 255—266. https://doi.org/10.1016/j.immuni.2016.06.015
PMid:27496731 PMCid:PMC4988931

15. 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. CellBio. 2; 2: 25—33. https://doi.org/10.4236/cellbio.2013.22006

15. Bou?as AP, Oliveira Fdos S, Canani LH, Crispim D. (2013). The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus. Arq Bras Endocrinol Metabol. 57; 9: 667—676.