Role of Orexin 1 Receptor Blocker SB-334867 On Changes Of Triglyceride And Cholesterol Metabolisminduced By Paradoxical Sleep Deprivation In Adult Male Rats

Ahmed, Hoda Mostafa; Mahmoud, Ahmed Mostafa; Ahmed, Mohammed Ashraf; Abdel-Sater, Khaled A.

doi:10.21608/smj.2019.45983

Role of Orexin 1 Receptor Blocker SB-334867 On Changes Of Triglyceride And Cholesterol Metabolisminduced By Paradoxical Sleep Deprivation In Adult Male Rats

Document Type : Original Article

Authors

¹ Department of Physiology, Faculty of Medicine, Sohag University, Sohag, Egypt.

² Department of Medical Physiology , Al-Azhar University (Assuit Branch).

10.21608/smj.2019.45983

Abstract

Background: Sleep deprivation (SD) is a growing hazard through its effects on metabolism. Orexin is involved in the regulation of both sleep and metabolism. Work on orexin receptors may explain the mechanisms of some hazardous effects of SD.
Aim: To test the role of the orexin-1 receptor (OX1R)blocker, SB-334867 in changes of triglycerides and cholesterol metabolisminduced by SD.
Method: 72 adult albino rats arranged in 4 equal groups: control, SD, SD-OX1R blocked &SD-DMSO groups. The 3 SD groups are subjected to 8 days of paradoxical SD using the modified multiple platform method. The OX1R blocked group was injected intraperitoneallydaily with a single dose (3 mg/kg/day) of SB-334867 dissolved in 2 ml DMSO and diluted 1:1000. The SD-DMSO group was injected by 2 ml of DMSO diluted 1:1000. Triglycerides and cholesterol levels were measured.
Results: Blood triglyceride levels dropped in all groups subjected to SD after the 1^stday while the blood cholesterol level dropped in all groups subjected to SD at the 7^th or 8^th day. In SD-OX1R blocked group showed less drop in blood triglycerides than the other SD groups but the statistically non-significant change in cholesterol level.
Conclusion: SD leads to earlier and more drop-in blood triglyceridesthan the drop in cholesterol levels. This can be explained by high metabolism during SD with dependence on triglyceride more than cholesterol. OX1R blocker partially reduces the drop of triglyceride, not cholesterol level indicating that orexin may be involved in the control of triglyceride metabolism but not cholesterol.

References

1. Pressman A, Hernandez A, Sikka SC. Chapter 5 - Lifestyle Stress and Its Impact on Male Reproductive Health. In: Sikka SC, Hellstrom WJG, editors. Bioenvironmental Issues Affecting Men's Reproductive and Sexual Health. Boston: Academic Press; 2018. p. 73-83.

2. Youngstedt SD, Goff EE, Reynolds AM, Kripke DF, Irwin MR, Bootzin RR, et al. Has Adult Sleep Duration Declined Over the Last 50+ Years? Sleep medicine reviews. 2016;28:69-85.

3. Jeddi S, Ghasemi A, Asgari A, Nezami-Asl A. Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats. Sleep and Breathing. 2018;22(2):353-9.

4. McHill AW, Wright KP. Role of sleep and circadian disruption on energy expenditure and metabolic predisposition to human obesity and metabolic disease. Obesity Reviews. 2017;18(S1):15-24.

5. Koren D, O’Sullivan KL, Mokhlesi B. Metabolic and glycemic sequelae of sleep disturbances in children and adults. Current diabetes reports. 2015;15(1):562.

6. Vetrivelan R, Fuller PM, Yokota S, Lu J, Saper CB. Metabolic effects of chronic sleep restriction in rats. Sleep. 2012;35(11):1511-20.

7. She M, Hu X, Su Z, Zhang C, Yang S, Ding L, et al. Piromelatine, a novel melatonin receptor agonist, stabilize metabolic profiles and ameliorates insulin resistance in chronic sleep-restricted rats. European journal of pharmacology. 2014;727:60-5.

8. Kargar HM-P, Azizi H, Mirnajafi-Zadeh J, Reza MA, Semnanian S. Microinjection of orexin-A into the rat locus coeruleus nucleus induces analgesia via cannabinoid type-1 receptors. Brain research. 2015;1624:424-32.

9. Villano I, Messina A, Valenzano A, Moscatelli F, Esposito T, Monda V, et al. Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention. Frontiers in Behavioral Neuroscience. 2017;11:10.

10. Brianza-Padilla M, Bonilla-Jaime H, Almanza-Pérez JC, López-López AL, Sánchez-Muñoz F, Vázquez-Palacios G. Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats. Applied Physiology, Nutrition, and Metabolism. 2015;41(3):235-43.

11. White C, Ishii Y, Mendoza T, Upton N, Stasi L, Bray G, et al. Effect of a selective OX1R antagonist on food intake and body weight in two strains of rats that differ in susceptibility to dietary-induced obesity. Peptides. 2005;26(11):2331-8.

12. Tsuneki H, Wada T, Sasaoka T. Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders. Pharmacology & therapeutics. 2017.

13. Andersen ML, Martins PJF, D'Almeida V, Santos RF, Bignotto M, Tufik S. Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Experimental Gerontology. 2004;39(5):817-24.

14. Alvarenga TA, Tufik S, Pires GN, Andersen ML. Influence of food restriction on lipid profile and spontaneous glucose levels in male rats subjected to paradoxical sleep deprivation. Clinics. 2012;67(4):375-80.

15. Messina A, De Fusco C, Monda V, Esposito M, Moscatelli F, Valenzano A, et al. Role of the orexin system on the hypothalamus-pituitary-thyroid axis. Frontiers in neural circuits. 2016;10:66.