Ukr.Biochem.J. 2018; Volume 90, Issue 5, Sep-Oct, pp. 81-90

doi: https://doi.org/10.15407/ubj90.05.081

The effect of N-stearoylethanolamine on adipocytes free cholesterol content and phospholipid composition in rats with obesity-induced insulin resistance

O. S. Dziuba, Ie. A. Hudz, H. V. Kosiakova, T. M. Horid’ko, V. M. Klimashevsky, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: oksana.dziuba86@gmail.com

Obesity induces molecular changes that promote associated disorders, such as insulin resistance (IR) and type 2 diabetes. Low insulin sensitivity occurs primarily due to defects in the pathway of insulin action in target tissues, and there is a hypothesis that IR may originate in adipose tissue and is followed by dyslipidemia. In this study using methods of thin-layer and gas-liquid chromatography we investigated free cholesterol content and phospholipid composition of adipocytes of obesity-induced IR rats and its changes induced by the N-stearoylethanolamine (NSE) administration. The results we obtained demonstrated that free cholesterol content significantly increased in adipocytes of IR rats compared to control. The analysis of phospholipid composition indicated a reduction of phosphatidylcholine and the total content of phosphatidylinositol with phosphatidylserine, whereas the content of lysophosphatidylcholine, sphingomyelin and phosphatidylethanolamine increased in IR group compared to control. NSE administration caused a statistically significant decrease in total cholesterol level and had a considerable effect on normalization of individual phospholipids content. As far as NSE administration caused a statistically significant decrease in free cholesterol level and had a considerable effect on normalization of individual phospholipids content of adipocytes, we can consider NSE as a prospective compound worthy more complex investigation of its action under the pathological conditions.

Keywords: , , , , ,


References:

  1. Eckel RH, Kahn SE, Ferrannini E, Goldfine AB, Nathan DM, Schwartz MW, Smith RJ, Smith SR. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? J Clin Endocrinol Metab. 2011 Jun;96(6):1654-63. PubMed, PubMedCentral, CrossRef
  2. Sears B, Perry M. The role of fatty acids in insulin resistance. Lipids Health Dis. 2015 Sep 29;14:121. PubMed, PubMedCentral, CrossRef
  3. Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014 Apr 11;15(4):6184-223.  PubMed, PubMedCentral, CrossRef
  4. Mittendorfer B. Origins of metabolic complications in obesity: adipose tissue and free fatty acid trafficking. Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):535-41.  PubMed, PubMedCentral, CrossRef
  5. Dawaliby R, Trubbia C, Delporte C, Noyon C, Ruysschaert JM, Van Antwerpen P, Govaerts C. Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells. J Biol Chem. 2016 Feb 12;291(7):3658-67.  PubMed, PubMedCentral, CrossRef
  6. Ohvo-Rekilä H, Ramstedt B, Leppimäki P, Slotte JP. Cholesterol interactions with phospholipids in membranes. Prog Lipid Res. 2002 Jan;41(1):66-97. PubMed, CrossRef
  7. Kosiakova GV, Gula NM. The N-stearoylethanolamine effect on the NO-synthase way of nitrogen oxide formation and phospholipid composition of erythrocyte membranes in rats with streptozotocine diabetes. Ukr Biokhim Zhurn. 2007 Nov-Dec;79(6):53-9. (In Ukrainian). PubMed
  8. Goridko TM, Gula NM, Stogniy NA, Meged OF, Klimashevsky VM, Shovkun SA, Kindruk NL, Berdyshev AG. Influence of N-stearoylethanolamine on the lipid peroxidation process and lipid composition of the rat liver under acute morphine intoxication. Ukr Biokhim Zhurn. 2007 Sep-Oct;79(5):175-85. (In Ukrainian). PubMed
  9. Gula NM, Chumak AA, Berdyshev AG, Meged EF, Goridko TM, Kindruk NL, Kosyakova GV, Zhukov OD. Anti-inflammatory effect of N-stearoylethanolamine on experimental burn wound in rats. Ukr Biokhim Zhurn. 2009 Mar-Apr;81(2):107-16. (In Ukrainian). PubMed
  10. Goridko TM, Kosiakova GV, Berdyschev AG, Bazylyanska VR, Margitich VM, Gula NM. The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes. Ukr Biokhim Zhurn. 2012 May-Jun;84(3):37-43. (In Ukrainian). PubMed
  11. Onopchenko OV, Kosiakova GV, Goridko TM, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity. Ukr Biochem J. 2014 Jan-Feb;86(1):101-10. (In Ukrainian). PubMed, CrossRef
  12. Onopchenko OV, Kosiakova GV, Oz M, Klimashevsky VM, Gula NM. N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats. Lipids. 2015 Jan;50(1):13-21.  PubMed, CrossRef
  13. Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol. 2006 Sep;169(3):846-60. PubMed, PubMedCentral, CrossRef
  14. Onopchenko OV, Kosiakova GV, Meged EF, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on cholesterol content, fatty acid composition and protein carbonylation level in rats with alimentary obesity-induced insulin resistance. Ukr Biochem J. 2014 Nov-Dec;86(6):119-28. PubMed, CrossRef
  15. Collier GR, Chisholm K, Sykes S, Dryden PA, O’Dea K. More severe impairment of oral than intravenous glucose tolerance in rats after eating a high fat diet. J Nutr. 1985 Nov;115(11):1471-6. PubMed, CrossRef
  16. Epps DE, Natarajan V, Schmid PC, Schmid HO. Accumulation of N-acylethanolamine glycerophospholipids in infarcted myocardium. Biochim Biophys Acta. 1980 Jun 23;618(3):420-30. PubMedCrossRef
  17. Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem. 1964 Feb;239:375-80. PubMed
  18. Mueller WM, Gregoire FM, Stanhope KL, Mobbs CV, Mizuno TM, Warden CH, Stern JS, Havel PJ. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology. 1998 Feb;139(2):551-8. PubMed, CrossRef
  19. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911-7. PubMed, CrossRef
  20. Vaskovsky VE, Terekhova TA. HPTLC of phospholipid mixtures containing phosphatidylglycerol. J High Resolut Chromatogr Chromatogr Commun. 1979; 2(11): 671–672. CrossRef
  21. Svetashev VI, Vaskovsky VE. A simplified technique for thin-layer microchromatography of lipids. J Chromatogr. 1972 May 3;67(2):376-8. PubMed, CrossRef
  22. Vaskovsky VE, Kostetsky EY, Vasendin IM. A universal reagent for phospholipid analysis. J Chromatogr. 1975 Nov 12;114(1):129-41. PubMed, CrossRef
  23. Cerqueira NM, Oliveira EF, Gesto DS, Santos-Martins D, Moreira C, Moorthy HN, Ramos MJ, Fernandes PA. Cholesterol Biosynthesis: A Mechanistic Overview. Biochemistry. 2016 Oct 4;55(39):5483-5506. PubMed, CrossRef
  24. Hussain MM, Strickland DK, Bakillah A. The mammalian low-density lipoprotein receptor family. Annu Rev Nutr. 1999;19:141-72. PubMed, CrossRef
  25. Marcuzzi A, Piscianz E, Loganes C, Vecchi Brumatti L, Knowles A, Bilel S, Tommasini A, Bortul R, Zweyer M. Innovative Target Therapies Are Able to Block the Inflammation Associated with Dysfunction of the Cholesterol Biosynthesis Pathway. Int J Mol Sci. 2015 Dec 30;17(1). pii: E47.  PubMed, PubMedCentral, CrossRef
  26. Rousset X, Vaisman B, Amar M, Sethi AA, Remaley AT. Lecithin: cholesterol acyltransferase–from biochemistry to role in cardiovascular disease. Curr Opin Endocrinol Diabetes Obes. 2009 Apr;16(2):163-71. PubMed, PubMedCentral, CrossRef
  27. Freeman M.W., Managing Your Cholesterol (Harvard Medical School Special Health Reports). Harvard Health Publications. 2015; 50 p.
  28. Yeagle PL. Cholesterol and the cell membrane. Biochim Biophys Acta. 1985 Dec 9;822(3-4):267-87. PubMed, CrossRef
  29. Fielding CJ, Fielding PE. Membrane cholesterol and the regulation of signal transduction. Biochem Soc Trans. 2004 Feb;32(Pt 1):65-9. PubMed, CrossRef
  30. Yeagle PL. Modulation of membrane function by cholesterol. Biochimie. 1991 Oct;73(10):1303-10. PubMed, CrossRef
  31. van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008 Feb;9(2):112-24. PubMed, PubMedCentral, CrossRef
  32. Zeghari N, Younsi M, Meyer L, Donner M, Drouin P, Ziegler O. Adipocyte and erythrocyte plasma membrane phospholipid composition and hyperinsulinemia: a study in nondiabetic and diabetic obese women. Int J Obes Relat Metab Disord. 2000 Dec;24(12):1600-7. PubMed, CrossRef
  33. Gavrilova NJ, Setchenska MS, Markovska TT, Momchilova-Pankova AB, Koumanov KS. Effect of membrane phospholipid composition and fluidity on rat liver plasma membrane tyrosine kinase activity. Int J Biochem. 1993 Sep;25(9):1309-12. PubMed, CrossRef
  34. Makdissy N, Haddad K, Mouawad C, Popa I, Younsi M, Valet P, Brunaud L, Ziegler O, Quilliot D.Regulation of SREBPs by Sphingomyelin in Adipocytes via a Caveolin and Ras-ERK-MAPK-CREB Signaling Pathway. PLoS One. 2015 Jul 31;10(7):e0133181. PubMed, PubMedCentral, CrossRef
  35. Macaulay SL, Larkins RG. Insulin stimulates turnover of phosphatidylcholine in rat adipocytes. Mol Cell Biochem. 1994 Jul 13;136(1):23-8. PubMed, CrossRef
  36. Donchenko V, Zannetti A, Baldini PM. Insulin-stimulated hydrolysis of phosphatidylcholine by phospholipase C and phospholipase D in cultured rat hepatocytes. Biochim Biophys Acta. 1994 Jul 21;1222(3):492-500. PubMed, CrossRef
  37. Cazzolli R, Huang P, Teng S, Hughes WE. Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and insulin-responsive muscle cells and adipocytes. Methods Mol Biol. 2009;462:241-51. PubMed, CrossRef
  38. Zolese G, Wozniak M, Mariani P, Saturni L, Bertoli E, Ambrosini A. Different modulation of phospholipase A2 activity by saturated and monounsaturated N-acylethanolamines. J Lipid Res. 2003 Apr;44(4):742-53. PubMed, PubMedCentral, CrossRef
  39. Cornell RB, Taneva SG. Amphipathic helices as mediators of the membrane interaction of amphitropic proteins, and as modulators of bilayer physical properties. Curr Protein Pept Sci. 2006 Dec;7(6):539-52. PubMed, CrossRef
  40. Slater SJ, Kelly MB, Taddeo FJ, Ho C, Rubin E, Stubbs CD. The modulation of protein kinase C activity by membrane lipid bilayer structure. J Biol Chem. 1994 Feb 18;269(7):4866-71.  PubMed
  41. Severson DL, Hurley B. Stimulation of the hormone-sensitive triacylglycerol lipase from adipose tissue by phosphatidylethanolamine. Biochim Biophys Acta. 1985 May 30;845(2):283-91. PubMed, CrossRef
  42. Matias I, Gonthier MP, Petrosino S, Docimo L, Capasso R, Hoareau L, Monteleone P, Roche R, Izzo AA, Di Marzo V. Role and regulation of acylethanolamides in energy balance: focus on adipocytes and beta-cells. Br J Pharmacol. 2007 Nov;152(5):676-90. PubMed, PubMedCentral, CrossRef
  43. Lambert DM, Muccioli GG. Endocannabinoids and related N-acylethanolamines in the control of appetite and energy metabolism: emergence of new molecular players. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):735-44. PubMed, CrossRef
  44. Artmann A, Petersen G, Hellgren LI, Boberg J, Skonberg C, Nellemann C, Hansen SH, Hansen HS. Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine. Biochim Biophys Acta. 2008 Apr;1781(4):200-12.  PubMed, CrossRef
  45. Mosior M, Newton AC. Mechanism of the apparent cooperativity in the interaction of protein kinase C with phosphatidylserine. Biochemistry. 1998 Dec 8;37(49):17271-9. PubMed, CrossRef
  46. Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert ML, Quon MJ, Lea-Currie R, Sen A, Farese RV. PKC-zeta mediates insulin effects on glucose transport in cultured preadipocyte-derived human adipocytes. J Clin Endocrinol Metab. 2002 Feb;87(2):716-23. PubMed, CrossRef
  47. Sweet LJ, Dudley DT, Pessin JE, Spector AA. Phospholipid activation of the insulin receptor kinase: regulation by phosphatidylinositol. FASEB J. 1987 Jul;1(1):55-9. PubMed, CrossRef
  48. Onopchenko OV, Kosiakova GV, Goridko TM, Berdyshev AG, Mehed OF, Hula NM. The effect of N-stearoylethanolamine on the activity of antioxidant enzymes, content of lipid peroxidation products and nitric oxide in the blood plasma and liver of rats with induced insulin-resistance. Ukr Biokhim Zhurn. 2013 Sep-Oct;85(5):88-96. (In Ukrainian). PubMed, CrossRef
  49. Newman JL, Stiers DL, Anderson WH, Schmid HH. Phase behavior of synthetic N-acylethanolamine phospholipids. Chem Phys Lipids. 1986 Dec 31;42(4):249-60. PubMed, CrossRef

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