DOI QR코드

DOI QR Code

Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats

  • Received : 2016.04.07
  • Accepted : 2016.07.27
  • Published : 2016.09.30

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and ${\beta}$-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

Keywords

References

  1. Laguna JC, Alegret M, Roglans N. 2014. Simple sugar intake and hepatocellular carcinoma: epidemiological and mechanistic insight. Nutrients 6: 5933-5954. https://doi.org/10.3390/nu6125933
  2. Cave M, Deaciuc I, Mendez C, Song Z, Joshi-Barve S, Barve S, McClain C. 2007. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem 18: 184-195. https://doi.org/10.1016/j.jnutbio.2006.12.006
  3. Dongiovanni P, Lanti C, Riso P, Valenti L. 2016. Nutritional therapy for nonalcoholic fatty liver disease. J Nutr Biochem 29: 1-11. https://doi.org/10.1016/j.jnutbio.2015.08.024
  4. Goran MI, Walker R, Allayee H. 2012. Genetic-related and carbohydrate-related factors affecting liver fat accumulation. Curr Opin Clin Nutr Metab Care 15: 392-396. https://doi.org/10.1097/MCO.0b013e3283544477
  5. Ferder L, Ferder MD, Inserra F. 2010. The role of high-fructose corn syrup in metabolic syndrome and hypertension. Curr Hypertens Rep 12: 105-112. https://doi.org/10.1007/s11906-010-0097-3
  6. Pool-Zobel BL, Bub A, Liegibel UM, Treptow-van Lishaut S, Rechkemmer G. 1998. Mechanisms by which vegetable consumption reduces genetic damage in humans. Cancer Epidemiol Biomarkers Prev 7: 891-899.
  7. Sharma KD, Karki S, Thakur NS, Attri S. 2012. Chemical composition, functional properties and processing of carrot-a review. J Food Sci Technol 49: 22-32. https://doi.org/10.1007/s13197-011-0310-7
  8. Potter AS, Foroudi S, Stamatikos A, Patil BS, Deyhim F. 2011. Drinking carrot juice increases total antioxidant status and decreases lipid peroxidation in adults. Nutr J 10: 96. https://doi.org/10.1186/1475-2891-10-96
  9. Torronen R, Lehmusaho M, Hakkinen S, Hanninen O, Mykkanen H. 1996. Serum ${\beta}$-carotene response to supplementation with raw carrots, carrot juice or purified ${\beta}$-carotene in healthy non-smoking women. Nutr Res 16: 565-575. https://doi.org/10.1016/0271-5317(96)00035-8
  10. Bub A, Watzl B, Abrahamse L, Delincee H, Adam S, Wever J, Muller H, Rechkemmer G. 2000. Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men. J Nutr 130: 2200-2206. https://doi.org/10.1093/jn/130.9.2200
  11. He Y, Root MM, Parker RS, Campbell TC. 1997. Effects of carotenoid-rich food extracts on the development of preneoplastic lesions in rat liver and on in vivo and in vitro antioxidant status. Nutr Cancer 27: 238-244. https://doi.org/10.1080/01635589709514532
  12. Kobaek-Larsen M, Christensen LP, Vach W, Ritskes-Hoitinga J, Brandt K. 2005. Inhibitory effects of feeding with carrots or (-)-falcarinol on development of azoxymethane-induced preneoplastic lesions in the rat colon. J Agric Food Chem 53: 1823-1827. https://doi.org/10.1021/jf048519s
  13. Pool-Zobel BL, Bub A, Muller H, Wollowski I, Rechkemmer G. 1997. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis 18: 1847-1850. https://doi.org/10.1093/carcin/18.9.1847
  14. Wehbe K, Mroueh M, Daher CF. 2009. The potential role of Daucus carota aqueous and methanolic extracts on inflammation and gastric ulcers in rats. J Complementary Integr Med 6: 7.
  15. Poudyal H, Panchal S, Brown L. 2010. Comparison of purple carrot juice and ${\beta}$-carotene in a high-carbohydrate, high-fat diet-fed rat model of the metabolic syndrome. Br J Nutr 104: 1322-1332. https://doi.org/10.1017/S0007114510002308
  16. Nicolle C, Gueux E, Lab C, Jaffrelo L, Rock E, Mazur A, Amouroux P, Remesy C. 2004. Lyophilized carrot ingestion lowers lipemia and beneficially affects cholesterol metabolism in cholesterol-fed C57BL/6J mice. Eur J Nutr 43: 237-245.
  17. Nicolle C, Cardinault N, Aprikian O, Busserolles J, Grolier P, Rock E, Demigne C, Mazur A, Scalbert A, Amouroux P, Remesy C. 2003. Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat. Eur J Nutr 42: 254-261. https://doi.org/10.1007/s00394-003-0419-1
  18. Sulaeman A, Keeler L, Giraud DW, Taylor SL, Wehling RL, Driskell JA. 2001. Carotenoid content and physicochemical and sensory characteristics of carrot chips deep-fried in different oils at several temperatures. J Food Sci 66: 1257-1264. https://doi.org/10.1111/j.1365-2621.2001.tb15198.x
  19. Nierenberg DW, Nann SL. 1992. A method for determining concentrations of retinol, tocopherol, and five carotenoids in human plasma and tissue samples. Am J Clin Nutr 56: 417-426. https://doi.org/10.1093/ajcn/56.2.417
  20. Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR. 1998. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2: 559-569. https://doi.org/10.1016/S1097-2765(00)80155-0
  21. Raja Gopal Reddy M, Pavan Kumar C, Mahesh M, Sravan Kumar M, Mullapudi Venkata S, Putcha UK, Vajreswari A, Jeyakumar SM. 2016. Vitamin A deficiency suppresses high fructose-induced triglyceride synthesis and elevates resolvin D1 levels. Biochim Biophys Acta 1861: 156-165. https://doi.org/10.1016/j.bbalip.2015.11.005
  22. Karahashi M, Ishii F, Yamazaki T, Imai K, Mitsumoto A, Kawashima Y, Kudo N. 2013. Up-regulation of stearoyl-CoA desaturase 1 increases liver MUFA content in obese zucker but not Goto-Kakizaki rats. Lipids 48: 457-467. https://doi.org/10.1007/s11745-013-3786-2
  23. Li ZZ, Berk M, McIntyre TM, Feldstein AE. 2009. Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 284: 5637-5644. https://doi.org/10.1074/jbc.M807616200
  24. Jeyakumar SM, Lopamudra P, Padmini S, Balakrishna N, Giridharan NV, Vajreswari A. 2009. Fatty acid desaturation index correlates with body mass and adiposity indices of obesity in Wistar NIN obese mutant rat strains WNIN/Ob and WNIN/GR-Ob. Nutr Metab 6: 27. https://doi.org/10.1186/1743-7075-6-27
  25. Miyazaki M, Dobrzyn A, Man WC, Chu K, Sampath H, Kim HJ, Ntambi JM. 2004. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem 279: 25164-25171. https://doi.org/10.1074/jbc.M402781200
  26. Stone RL, Bernlohr DA. 1990. The molecular basis for inhibition of adipose conversion of murine 3T3-L1 cells by retinoic acid. Differentiation 45: 119-127. https://doi.org/10.1111/j.1432-0436.1990.tb00465.x
  27. Miller CW, Waters KM, Ntambi JM. 1997. Regulation of hepatic stearoyl-CoA desaturase gene 1 by vitamin A. Biochem Biophys Res Commun 231: 206-210. https://doi.org/10.1006/bbrc.1997.6070
  28. Jeyakumar SM, Vajreswari A, Giridharan NV. 2008. Vitamin A regulates obesity in WNIN/Ob obese rat; independent of stearoyl-CoA desaturase-1. Biochem Biophys Res Commun 370: 243-247. https://doi.org/10.1016/j.bbrc.2008.03.073
  29. Ntambi JM, Miyazaki M. 2004. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res 43: 91-104. https://doi.org/10.1016/S0163-7827(03)00039-0
  30. Heinemann FS, Ozols J. 1998. Degradation of stearoyl-coenzyme A desaturase: endoproteolytic cleavage by an integral membrane protease. Mol Biol Cell 9: 3445-3453. https://doi.org/10.1091/mbc.9.12.3445
  31. Heinemann FS, Ozols J. 2003. Stearoyl-CoA desaturase, a short-lived protein of endoplasmic reticulum with multiple control mechanisms. Prostaglandins Leukot Essent Fatty Acids 68: 123-133. https://doi.org/10.1016/S0952-3278(02)00262-4
  32. Heinemann FS, Korza G, Ozols J. 2003. A plasminogen-like protein selectively degrades stearoyl-CoA desaturase in liver microsomes. J Biol Chem 278: 42966-42975. https://doi.org/10.1074/jbc.M306240200
  33. Heinemann FS, Mziaut H, Korza G, Ozols J. 2003. A microsomal endopeptidase from liver that preferentially degrades stearoyl-CoA desaturase. Biochemistry 42: 6929-6937. https://doi.org/10.1021/bi034071x
  34. Fan J, Krautkramer KA, Feldman JL, Denu JM. 2015. Metabolic regulation of histone post-translational modifications. ACS Chem Biol 10: 95-108. https://doi.org/10.1021/cb500846u
  35. Hanes SD. 2015. Prolyl isomerases in gene transcription. Biochim Biophys Acta 1850: 2017-2034. https://doi.org/10.1016/j.bbagen.2014.10.028
  36. Lee J, Ozcan U. 2014. Unfolded protein response signaling and metabolic diseases. J Biol Chem 289: 1203-1211. https://doi.org/10.1074/jbc.R113.534743
  37. Guillou H, Zadravec D, Martin PG, Jacobsson A. 2010. The key roles of elongases and desaturases in mammalian fatty acid metabolism: insights from transgenic mice. Prog Lipid Res 49: 186-199. https://doi.org/10.1016/j.plipres.2009.12.002
  38. Raja Gopal Reddy M, Asha GV, Sravan Kumar M, Uday Kumar P, Vajreswari A, Jeyakumar SM. 2016. High fat diet feeding elevates liver retinol, docosahexaenoic acid and very long chain fatty acid elongase 2 levels in C57BL/6J mice. Int J Vitam Nutr Res (In press).
  39. Pauter AM, Olsson P, Asadi A, Herslof B, Csikasz RI, Zadravec D, Jacobsson A. 2014. Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice. J Lipid Res 55: 718-728. https://doi.org/10.1194/jlr.M046151
  40. Zheng J, Peng C, Ai Y, Wang H, Xiao X, Li J. 2016. Docosahexaenoic acid ameliorates fructose-induced hepatic steatosis involving ER stress response in primary mouse hepatocytes. Nutrients 8: 55. https://doi.org/10.3390/nu8010055
  41. Soni NK, Nookaew I, Sandberg A, Gabrielsson BG. 2015. Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice. Lipids Health Dis 14: 74. https://doi.org/10.1186/s12944-015-0072-8
  42. Depner CM, Philbrick KA, Jump DB. 2013. Docosahexaenoic acid attenuates hepatic inflammation, oxidative stress, and fibrosis without decreasing hepatosteatosis in a $Ldlr^{-/-}$ mouse model of western diet-induced nonalcoholic steatohepatitis. J Nutr 143: 315-323. https://doi.org/10.3945/jn.112.171322
  43. Fedor DM, Adkins Y, Mackey BE, Kelley DS. 2012. Docosahexaenoic acid prevents trans-10, cis-12-conjugated linoleic acid-induced nonalcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation. Metab Syndr Relat Disord 10: 175-180. https://doi.org/10.1089/met.2011.0113
  44. Nobili V, Bedogni G, Alisi A, Pietrobattista A, Rise P, Galli C, Agostoni C. 2011. Docosahexaenoic acid supplementation decreases liver fat content in children with non- alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child 96: 350-353. https://doi.org/10.1136/adc.2010.192401
  45. Janczyk W, Socha P, Lebensztejn D, Wierzbicka A, Mazur A, Neuhoff-Murawska J, Matusik P. 2013. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial. BMC Pediatr 13: 85. https://doi.org/10.1186/1471-2431-13-85

Cited by

  1. Carrot juice ingestion attenuates high fructose-induced circulatory pro-inflammatory mediators in weanling Wistar rats vol.97, pp.5, 2017, https://doi.org/10.1002/jsfa.7906
  2. Transcription profiling in the liver of undernourished male rat offspring reveals altered lipid metabolism pathways and predisposition to hepatic steatosis vol.317, pp.6, 2019, https://doi.org/10.1152/ajpendo.00291.2019
  3. Folic acid supplementation prevents high fructose-induced non-alcoholic fatty liver disease by activating the AMPK and LKB1 signaling pathways vol.14, pp.4, 2020, https://doi.org/10.4162/nrp.2020.14.4.309
  4. Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα vol.28, pp.None, 2021, https://doi.org/10.1051/ocl/2021030
  5. Carrot Juice Consumption Reduces High Fructose-Induced Adiposity in Rats and Body Weight and BMI in Type 2 Diabetic Subjects vol.14, pp.None, 2016, https://doi.org/10.1177/11786388211014917