Early oleate deficiency leads to severe defects in fetal rat liver development

Document Type : Original Article

Authors

1 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

4 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

5 Comprehensive Health Lab, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective(s): Oleate can be produced through de novo synthesis, which contributes to biological processes and signaling pathways. However, the role of this non-essential fatty acid in hepatic development remains unclear. The current study aimed to evaluate the influence of early oleate deficiency induced by the inhibitor of de novo oleate synthesis MF-438 on fetal rat liver development.
Materials and Methods: Female Wistar rats with an average weight of 200±20 g were subjected to this study. After mating, pregnant rats were divided into three groups and gavaged with the vehicle, MF 438 or MF-438 plus oleate from day 3 of pregnancy for five days. Obtained fetuses were sacrificed and the liver tissues were retrieved. Hepatic morphological index, biochemical markers, and gene expression of hepatic development markers were analyzed using Hematoxylin-Eosine, spectrometry, and real-time PCR techniques, respectively.
Results: Relatively, deficient morphological indices and hepatic maturation markers were observed in fetus livers of the inhibitor-treated group. In comparison to the other two groups, total hepatic protein and glycogen content were increased with treatment of MF-438 plus oleate. Hepatocyte nuclear factor 1α, alpha fetoprotein, albumin, and cytochrome P450 gene expression were also significantly increased in the group treated with both MF-438 and oleate.
Conclusion: Our data indicate that oleate availability during early embryo development is linked with fetal rat liver development.

Keywords

Main Subjects


1. Gruppuso PA, Sanders JA. Regulation of liver development: implications for liver biology across the lifespan. J Mol Endocrinol 2016; 56:115-125.
2. Maisels MJ, Kring E. The contribution of hemolysis to early jaundice in normal newborns. Pediatr 2006; 118: 276-279.
3. Ducheix S, Montagner A, Polizzi A, Lasserre F, Régnier M, Marmugi A, et al. Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling. PLoS One 2017; 12: e0181393.
4. Burhans MS, Flowers MT, Harrington KR, Bond LM, Guo C-A, Anderson RM, et al. Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation. J Lipid Res 2015; 56:304-318.
5. Lee JY, Moon JH, Park JS, Lee B-W, Kang ES, Ahn CW, et al. Dietary oleate has beneficial effects on every step of non-alcoholic Fatty liver disease progression in a methionine-and choline-deficient diet-fed animal model. Diabetes Metab J 2011; 35: 489-496.
6. Miyazaki M, Kim Y-C, Gray-Keller MP, Attie AD, Ntambi JM. The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in mice with a disruption of the gene for stearoyl-CoA desaturase 1. J Biol Chem 2000; 275: 30132-30138.
7. Zhang L, Ge L, Parimoo S, Stenn K, Prouty SM. Human stearoyl-CoA desaturase: alternative transcripts generated from a single gene by usage of tandem polyadenylation sites. Biochem J 1999; 340: 255-264.
8. Mardomi A, Nouri M, Farzadi L, Zarghami N, Mehdizadeh A, Yousefi M, et al. Human charcoal-stripped serum supplementation enhances both the stearoyl-coenzyme a desaturase 1 activity of cumulus cells and the in vitro maturation of oocytes. Hum Fertil 2018; 1-7.
9. Rahimi Y, Mehdizadeh A, Nozad Charoudeh H, Nouri M, Valaei K, Fayezi S, et al. Hepatocyte differentiation of human induced pluripotent stem cells is modulated by stearoyl‐CoA desaturase 1 activity. Dev Growth Differ 2015; 57: 667-674.
10. Song G, Pacher M, Balakrishnan A, Yuan Q, Tsay H-C, Yang D, et al. Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis. Cell Stem Cell 2016; 18: 797-808.
11. Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res 1991; 51: 2611-2620.
12. Rios-Esteves J, Resh MD. Stearoyl CoA desaturase is required to produce active, lipid-modified Wnt proteins. Cell Rep 2013; 4: 1072-1081.
13. Ralston J, Badoud F, Cattrysse B, McNicholas P, Mutch D. Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis. Int J Obes 2014; 38: 1449-1456.
14. Sen S, Jumaa H, Webster NJ. Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function. Nat Commun 2013; 4: 1336.
15. Caligioni CS. Assessing reproductive status/stages in mice. Curr Protoc Neurosci 2009; 48: A. 4I. 1-A. 4I. 8.
16. Sampath H, Flowers MT, Liu X, Paton CM, Sullivan R, Chu K, et al. Skin-specific deletion of stearoyl-CoA desaturase-1 alters skin lipid composition and protects mice from high-fat diet-induced obesity. J Biol Chem 2009; 284:19961-19973.
17. Stoffel W, Schmidt-Soltau I, Jenke B, Binczek E, Hammels I. Hair Growth Cycle Is Arrested in SCD1 Deficiency by Impaired Wnt3a-Palmitoleoylation and Retrieved by the Artificial Lipid Barrier. J Invest Dermatol 2017; 137: 1424-1433.
18. Zhang P. Analysis of mouse liver glycogen content. Bio Protoc 2012; 2: e186.
19. Waterborg JH. The Lowry method for protein quantitation.  The protein protocols handbook: Springer; 2009. p. 7-10.
20. Lee H, Lim JY, Choi SJ. Role of l-carnitine and oleate in myogenic differentiation: implications for myofiber regeneration. J Exerc Nutrition Biochem 2018; 22: 36-42.
21. Chen CT, Hsu SH, Wei YH. Mitochondrial bioenergetic function and metabolic plasticity in stem cell differentiation and cellular reprogramming. Biochim Biophys Acta Gen Subj 2012; 1820: 571-576.
22. Xu X, Duan S, Yi F, Ocampo A, Liu GH, Belmonte JCI. Mitochondrial regulation in pluripotent stem cells. Cell Metab 2013; 18: 325-332.
23. Cho YM, Kwon S, Pak YK, Seol HW, Choi YM, Park DJ, et al. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem Biophys Res Commun 2006; 348: 1472-1478.
24. Lonergan T, Bavister B, Brenner C. Mitochondria in stem cells. Mitochondrion 2007; 7: 289-296.
25. Yuzefovych L, Wilson G, Rachek L. Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress. Am J Physiol Endocrinol Metab 2010; 299: E1096-E1105.
26. Briolay A, Jaafar R, Nemoz G, Bessueille L. Myogenic differentiation and lipid-raft composition of L6 skeletal muscle cells are modulated by PUFAs. Biochim Biophys Acta Biomembr 2013; 1828: 602-613.
27. Leekumjorn S, Cho HJ, Wu Y, Wright NT, Sum AK, Chan C. The role of fatty acid unsaturation in minimizing biophysical changes on the structure and local effects of bilayer membranes. Biochim Biophys Acta Biomembr 2009; 1788: 1508-1516.
28. Aardema H, van Tol HT, Wubbolts RW, Brouwers JF, Gadella BM, Roelen BA. Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress. Biol Reprod 2017; 96: 982-992.