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Molecular bases of the development of obesity and its metabolic complications in children

SOVREMENNAYA PEDIATRIYA. 2015.2(66):109-112; doi 10.15574/SP.2015.65.109

 

Molecular bases of the development of obesity and its metabolic complications in children

 

Minchenko D. O.

Department of Pediatrics №1, National O.O. Bohomolets Medical University, Kyiv, Ukraine;

Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kyiv, Ukraine;

 

The goal of this study was to analyze the literature sources concerning molecular bases of the development of obesity and its complications associated with insulin resistance in children and adolescents. It was shown by multiple investigations that the development of obesity and its metabolic complications is preferentially conditioned by environment factors, dysregulation of biological rhythms and genetic background. Special interest is applicate to biological clock dysregulation, which controls the most physiological and metabolic processes and tightly connected to endoplasmic reticulum stress. This stress provides the adaptation of cells to various changes of homeostasis and is related to the development of obesity, insulin resistance and type 2 diabetes. Possibility of the creation of novel compounds and therapeutic strategies to manipulate levels of endoplasmic reticulum stress in various diseases including obesity is discussed.

 

Key words: obesity, insulin resistance, biological clock, endoplasmic reticulum stress, children.

 

REFERENCES

1. Тяжка ОВ, Мінченко ДО, Молявко ОС та ін. 2014. Експресія генів ALDOC, TIGAR, ENO1 та ENO2 у клітинах крові дітей чоловічої статі з ожирінням, ускладненим резистентністю до інсуліну. Суч педіатрія. 6(62): 112—115.

2. 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.

3. 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.

4. Ailhaud G, Guesnet P et al. 2004. Fatty acid composition of fats is an early determinant of childhood obesity: a short review and an opinion. Obes Rev. 5;1: 21—26.

5. Vieira E, Ruano EG, Figueroa ALC et al. 2014. Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome. PLoS One. 9;11: e111678.

6. Bray MS, Young ME. 2009. The role of cell-specific circadian clocks in metabolism and disease. Obes Rev. 10;Suppl 2: 6—13.

7. Cao SS, Kaufman RJ. 2013. Targeting endoplasmic reticulum stress in metabolic disease. Expert Opin Ther Targets. 17;4: 437—448.

8. Prats-Puig A, Ortega FJ, Mercader JM et al. 2013. Changes in circulating microRNAs are associated with childhood obesity. J Clin Endocrinol Metab. 98;10: 1655—1660.

9. Pappa KI, Gazouli M, Anastasiou E et al. 2013. Circadian clock gene expression is impaired in gestational diabetes mellitus. Gynecol Endocrinol. 29;4: 331—335.

10. Milagro FI, Gomez-Abellan P, Campion J et al. 2012. CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol Int. 29;9: 1180—1194.

11. Zhou B, Zhang Y, Zhang F et al. 2014. CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1. Hepatology. 59;6: 2196—2206.

12. Menet JS, Pescatore S, Rosbash M et al. 2014. CLOCK:BMAL1 is a pioneer-like transcription factor. Genes Dev. 28;1: 8—13.

13. Pepin E, Higa A, Schuster-Klein C et al. 2014. Deletion of apoptosis signal-regulating kinase 1 (ASK1) protects pancreatic beta-cells from stress-induced death but not from glucose homeostasis alterations under pro-inflammatory conditions. PLoS One. 9;11: e112714.

14. Oosting A, van Vlies N, Kegler D et al. 2014. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood. Br J Nutr. 111;2: 215—226.

15. Ozcan U, Cao Q, Yilmaz E et al. 2004. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 306: 457—461.

16. Minchenko OH, Bashtа YM, Minchenko DO et al. 2014. Expression of genes, which control proliferation processes, in subcutaneous adipose tissue of the obese men with glucose intolerance. Appl Cell Biol. 3;4: 120—128.

17. Han J, Kaufman RJ. 2014. Measurement of the unfolded protein response to investigate its role in adipogenesis and obesity. Methods Enzymol. 538: 135—150.

18. Huang W, Ramsey KM, Marcheva B, Bass J. 2011. Circadian rhythms, sleep, and metabolism. J Clin Invest. 121: 2133—2141.

19. Tiazhka OV, Minchenko DO, Davydov VV et al. 2014. Insulin resistance affects the expression of genes related to the control of cell growth and surviving in blood cells of obese boys. Biol Systems. 6;2: 120—126.

20. Kennaway DJ, Varcoe TJ, Voultsios A, Boden MJ. 2013. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism. PLoS One. 8;6: 65255.

21. Lee J, Ozcan U. 2014. Unfolded protein response signaling and metabolic diseases. J Biol Chem. 289;3: 1203—1211.

22. Manie SN, Lebeau J, Chevet E. 2014. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update. Am J Physiol Cell Physiol. 307;10: C901—907.

23. Martos-Moreno GA, Barrios V, Chowen JA, Argente J et al. 2013. Adipokines in childhood obesity. Vitam Horm. 91: 107—142.

24. Chen YC, Colvin ES, Maier BF et al. 2013. Mitogen-inducible gene 6 triggers apoptosis and exacerbates ER stress-induced β-cell death. Mol Endocrinol. 27;1: 162—171.

25. Minchenko OH, Kubaichuk KI, Minchenko DO et al. 2014. Molecular mechanisms of ERN1-mediated angiogenesis. Int J Physiol Pathophysiol. 5;1: 1—22.

26. Paschos GK, Ibrahim S, Song WL et al. 2012. Obesity in mice with adipocyte-specific deletion of clock component Arntl. Nat Med. 18;12: 1768—1777.

27. Lee J, Sun C, Zhou Y et al. 2011. P38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med. 17: 1251—1260.

28. Balakrishnan A, Stearns AT, Ashley SW et al. 2012. PER1 modulates SGLT1 transcription in vitro independent of E-box status. Dig Dis Sci. 57: 1525—1536.

29. Grimaldi B, Bellet MM, Katada S et al. 2010. PER2 controls lipid metabolism by direct regulation of PPAR-. Cell Metab. 12: 509—520.

30. Rastogi D, Suzuki M, Greally JM. 2013. Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma. Sci Rep. 3: 2164.

31. Mejia-Barradas CM, Del-Rio-Navarro BE, Dominguez-Lopez A et al. 2014. The consumption of n-3 polyunsaturated fatty acids differentially modulates gene expression of peroxisome proliferator-activated receptor alpha and gamma and hypoxia-inducible factor 1 alpha in subcutaneous adipose tissue of obese adolescents. Endocrine. 45;1: 98—105.

32. 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.

33. Trayhurn P. 2013. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev. 93;1: 1—21.

34. Toedebusch RG, Roberts MD, Wells KD et al. 2014. Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity. Physiol Genomics. 46;10: 362—375.

35. Wang S, Kaufman RJ. 2014. How does protein misfolding in the endoplasmic reticulum affect lipid metabolism in the liver? Curr Opin Lipidol. 25;2: 125—132.