Volume 10, Issue 3 (Vol.10 No.3 Oct 2021)                   rbmb.net 2021, 10(3): 437-444 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Dewi S, Yulhasri Y, Mulyawan W. The Impact of Intermittent Hypobaric Hypoxia Exposures on Triacylglycerol Synthesis in Rat Liver. rbmb.net. 2021; 10 (3) :437-444
URL: http://rbmb.net/article-1-688-en.html
Department of Biochemistry and Molecular Biology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia & Center of Hypoxia and Oxidative Stress Studies, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
Abstract:   (387 Views)
Background: In a hypoxic state, fatty acid breakdown reaction may be inhibited due to a lack of oxygen. It is likely that the fatty acids will be stored as triacylglycerol. The aim of this study was to analyse triacylglycerol synthesis in the liver after intermittent hypobaric hypoxia (HH) exposures.

Methods: Samples are liver tissues from 25 male Wistar rats were divided into 5 groups: control group (normoxia), group I (once HH exposure), group II (twice HH exposures), group III (three-times HH exposures) and group IV (four-times HH exposures). The triacylglycerol level, mRNA expression
of HIF-1α and PPAR-γ were measured in rat liver from each group.

Results: We demonstrated that triacylglycerol level, mRNA expression of HIF-1α and PPAR-γ is elevated in group I significantly compared to control group. In the intermittent HH groups (group II, III and IV), mRNA expression of HIF-1α and PPAR-γ tends to downregulate near to control group. However, the triacylglycerol level is still found increased in the intermittent HH exposures groups. Significant increasing of triacylglycerol level was found especially in group IV compared to control group. 

Conclusions: We conclude that intermittent HH exposures will increase the triacylglycerol level in rat liver, supported by the increasing of HIF-1α and PPAR-γ mRNA expression that act as  transcription factor to promote triacylglycerol synthesis.
Full-Text [PDF 283 kb]   (203 Downloads)    
Type of Article: Original Article | Subject: Biochemistry
Received: 2021/04/19 | Accepted: 2021/05/23 | Published: 2021/12/5

1. Alves-Bezerra M, Cohen DE. Triglyceride metabolism in the liver. Compr Physiol. 2018;8(1):1-8. [DOI:10.1002/cphy.c170012] [PMID] [PMCID]
2. Lieberman M, Peet A. Marks' basic medical biochemistry: a clinical approach. 5th edition. Philadelphia: Wolters Kluwer; 2018. 433-471.
3. Mylonis I, Simos G, Paraskeva E. Hypoxia-Inducible Factors and the Regulation of Lipid Metabolism. Cells. 2019;8(3):214. [DOI:10.3390/cells8030214] [PMID] [PMCID]
4. Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C, et al. Activation of a HIF1α-PPARγ Axis Underlies the Integration of Glycolytic and Lipid Anabolic Pathways in Pathologic Cardiac Hypertrophy. Cell Metab. 2009;9(6):512-24. [DOI:10.1016/j.cmet.2009.05.005] [PMID]
5. Koh MY, Spivak-Kroizman T, Powis G. HIF-1 regulation: not so easy come, easy go. Trends Biochem Sci. 2008;33(11):526-34. [DOI:10.1016/j.tibs.2008.08.002] [PMID]
6. Weidemann A, Johnson RS. Biology of HIF-1α. Cell Death Differ. 2008;15(4):621-7. [DOI:10.1038/cdd.2008.12] [PMID]
7. Shen G, Li X. The Multifaceted Role of Hypoxia‐Inducible Factor 1 (HIF1). In: Lipid Metabolism, Hypoxia and Human Diseases, Jing Zheng J, Zhou, Ch. IntechOpen; 2017. p. 1-29. [DOI:10.5772/65340]
8. Sarkar S, Banerjee PK, Selvamurthy W. High altitude hypoxia: An intricate interplay of oxygen responsive macroevents and micromolecules. Mol Cell Biochem. 2003;253(1-2):287-305. [DOI:10.1023/A:1026080320034] [PMID]
9. Tirosh O. Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression. Oxid Med Cell Longev. 2018;2018:2548154. [DOI:10.1155/2018/2548154] [PMID] [PMCID]
10. Wald A, Fay C, Gleich R. Introduction to Aviation Management. 2010.
11. Maresh RW, Woodrow AD, Webb JT. Handbook of Aerospace and Operational Physiology, 2nd Edition. 2018. 1-842 p.
12. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8. [DOI:10.1006/meth.2001.1262] [PMID]
13. Triantafyllou E-A, Georgatsou E, Mylonis I, Simos G, Paraskeva E. Expression of AGPAT2, an enzyme involved in the glycerophospholipid/triacylglycerol biosynthesis pathway, is directly regulated by HIF-1 and promotes survival and etoposide resistance of cancer cells under hypoxia. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(9):1142-52. [DOI:10.1016/j.bbalip.2018.06.015] [PMID]
14. Mylonis I, Sembongi H, Befani C, Liakos P, Siniossoglou S, Simos G. Hypoxia causes triglyceride accumulation by HIF-1-mediated stimulation of lipin 1 expression. J Cell Sci. 2012;125(Pt 14):3485-93. [DOI:10.1242/jcs.106682] [PMID] [PMCID]
15. Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, et al. Lipin 1 is an inducible amplifier of the hepatic PGC-1α/PPARα; regulatory pathway. Cell Metab. 2006;4(3):199-210. [DOI:10.1016/j.cmet.2006.08.005] [PMID]
16. Viscor G, Torrella JR, Corral L, Ricart A, Javierre C, Pages T, et al. Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications. Front Physiol. 2018;9:814. [DOI:10.3389/fphys.2018.00814] [PMID] [PMCID]
17. Zhao Y-Z, Liu X-L, Shen G-M, Ma Y-N, Zhang F-L, Chen M-T, et al. Hypoxia induces peroxisome proliferator-activated receptor γ expression via HIF-1-dependent mechanisms in HepG2 cell line. Arch Biochem Biophys. 2014;543:40-7. [DOI:10.1016/j.abb.2013.12.010] [PMID]
18. Shi H, Luo J, Zhu J, Li J, Sun Y, Lin X, et al. PPARγ Regulates Genes Involved in Triacylglycerol Synthesis and Secretion in PPAR Res. 2013;2013:310948. [DOI:10.1155/2013/310948] [PMID] [PMCID]
19. Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 1994;135(2):798-800. [DOI:10.1210/endo.135.2.8033830] [PMID]
20. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. PPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro. Mol Cell. 1999;4(4):611-7. [DOI:10.1016/S1097-2765(00)80211-7]
21. Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C, et al. Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab. 2009;9(6):512-24. [DOI:10.1016/j.cmet.2009.05.005] [PMID]
22. Matsusue K, Haluzik M, Lambert G, Yim S-H, Gavrilova O, Ward JM, et al. Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Invest. 2003;111(5):737-747. [DOI:10.1172/JCI200317223] [PMID] [PMCID]
23. Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol. 2006;290(5):G852-8. [DOI:10.1152/ajpgi.00521.2005] [PMID]
24. Etesami B, Ghaseminezhad S, Nowrouzi A, Rashidipour M, Yazdanparast R, et al. Investigation of 3T3-L1 Cell Differentiation to Adipocyte, Affected by Aqueous Seed Extract of Phoenix Dactylifera L. Reports Biochem Mol Biol. 2020;9(1):14-25. [DOI:10.29252/rbmb.9.1.14] [PMID] [PMCID]
25. Huang D, Li T, Li X, Zhang L, Sun L, He X, et al. HIF-1-Mediated Suppression of Acyl-CoA Dehydrogenases and Fatty Acid Oxidation Is Critical for Cancer Progression. Cell Rep. 2014;8(6):1930-1942. [DOI:10.1016/j.celrep.2014.08.028] [PMID]
26. Liu Y, Ma Z, Zhao C, Wang Y, Wu G, Xiao J, et al. HIF-1α and HIF-2α are critically involved in hypoxia-induced lipid accumulation in hepatocytes through reducing PGC-1α-mediated fatty acid β-oxidation. Toxicol Lett. 2014;226(2):117-23. [DOI:10.1016/j.toxlet.2014.01.033] [PMID]
27. Han JS, Lee JH, Kong J, Ji Y, Kim J, Choe SS, et al. Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor. Mol Cell Biol. 2019;39(2):e00390-18. [DOI:10.1128/MCB.00390-18]
28. Suzuki T, Shinjo S, Arai T, Kanai M, Goda N. Hypoxia and fatty liver. World J Gastroenterol. 2014;20(41):15087-15097. [DOI:10.3748/wjg.v20.i41.15087] [PMID] [PMCID]
29. Savage DB, Semple RK. Recent insights into fatty liver, metabolic dyslipidaemia and their links to insulin resistance. Curr Opin Lipidol. 2010;21(4):329-36. [DOI:10.1097/MOL.0b013e32833b7782] [PMID]
30. Aron-Wisnewsky J, Minville C, Tordjman J, Lévy P, Bouillot J-L, Basdevant A, et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol. 2012;56(1):225-33. [DOI:10.1016/j.jhep.2011.04.022] [PMID]
31. Sookoian S, Pirola CJ. Obstructive Sleep Apnea Is Associated with Fatty Liver and Abnormal Liver Enzymes: a Meta-analysis. Obes Surg. 2013;23(11):1815-25. [DOI:10.1007/s11695-013-0981-4] [PMID]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb