Histologic, Metabolic, and Inflammatory Changes in the Liver of High-fat Diet-induced Obese Rats before and after Vitamin D Administration

improved liver inflammation and injury by vitamin D

  • Mahdi Yaghchiyan Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Leila Roshangar Stem Cells Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Mahdieh Abbasalizad Farhangi Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Mehran Mesgari-Abbasi Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Leila Rafiei Department of Food Sciences and Technology, University of Urmia, Urmia, Iran
  • Parviz Shahabi Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords: Inflammation, Liver histology, Obesity, Vitamin D

Abstract

The current study aimed to investigate the effects of vitamin D administration on the markers of inflammation and metabolic damages in the liver of high-fat diet-induced obese rats. Forty male Wistar rats were divided into two groups of control receiving a normal diet (ND) and intervention receiving a high-fat diet (HFD). After 16 weeks, each group was divided into two groups including ND, ND + vitamin D, HFD, and HFD + vitamin D. Vitamin D was administered by oral gavage for five weeks at the dose of 500 IU/kg. Hepatic MCP-1, TGF-β, and NF-κB levels, serum liver enzymes, and serum lipids, and histological and structural changes in the liver were determined. Vitamin D administration significantly reduced the monocyte chemoattractant protein (MCP)-1 concentrations in the HFD + vitamin D group compared with the HFD group and reduced liver Transforming growth factor beta (TGF-β) levels in both vitamin D-treated groups (p<0.05). Moreover, a significant reduction in the serum levels of aspartate amino transferase (AST) and alanine amino transferase (ALT) in vitamin D treated groups was identified (p<0.05). A significant improvement in lipids and a pronounced improvement in the markers of liver histology damage including fat accumulation, aggregation of inflammatory cells, pre-apoptotic changes, hepatic sinusoidal dilatation, and necrotic pyknosis in the Kupffer cells were also identified. Our results demonstrated that vitamin D has potential effects in ameliorating the inflammatory, metabolic, and histologic changes in the liver of these animals.

References

1. Farhangi MA, Mesgari-Abbasi M, Hajiluian Gh, Nameni Gh, Shahabi P. Adipose tissue inflammation and oxidative stress: the ameliorative effects of vitamin D. Inflammation 2017; 40(5):1688-99.
2. Ramos EJ, Xu Y, Romanova I. Is obesity an inflamatuar disease? Surgery 2003; 134(2):329-35.
3. Hajiluian Gh, Abbasalizad-Farhangi M, Nameni G, Shahabi P, Megari-Abbasi M. Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration inrats. Nutr Neurosci 2018; 21(10):744-752.
4. Schuster N, Krieglstein K. Mechanisms of TGF-beta-mediated apoptosis. Cell Tissue Res 2002; 307(1):1-14.
5. Karlmark RK, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, et al. Hepatic recruitment of the inflammatory Gr 1 monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology 2009; 12: 261-74.
6. Tsuruta S, Nakamuta M, Enjoji M, Kotoh K, Hiasa K, Egashira K, et al. Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats. Int J Mol Med 2004; 14(5):837-42.
7. Elsharkawy AM, Mann DA. Nuclear Factor-B and the hepatic inflammation-fibrosis-cancer axis. Hepatology 2007; 46(2):590-7.
8. Sunami Y, Leithauser F, Gul S, Fiedler K, Guldiken N, Espenlaub S, et al. Hepatic activation of IKK/NFjB signaling induces liver fibrosis via macrophage-mediated chronic inflammation. Hepatology 2012; 56(3):1117-28.
9. Luedde T, Schwabe RF. NF-κB in the liver--linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2011; 8(2):108-18.
10. Borel P, Caillaud D, Cano NJ. Vitamin D bioavailability: state of the art. Crit Rev Food Sci Nutr 2015; 55(9):1193-205.
11. Kitson MT, Roberts SK. Delivering the message: The importance of vitamin D status in chronic liver disease. J Hepatol 2012; 57(4):897–909.
12. Konstantakis C, Tselekouni P, Kalafateli M, Triantos C. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol 2016; 29(3):297–306.
13. Skaaby T, Husemoen LL, Borglykke A, Jørgensen T, Thuesen BH, Pisinger C, et al. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine 2014; 47(1):213-20.
14. Chung GE, Kim D, Kwak MS, Yang JI, Yim JY, Lim SH, et al. The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease. Clin Mol Hepatol 2016; 22(1):146–51.
15. Hajiluian G, Nameni G, Shahabi P, Mesgari-Abbasi M, Sadigh-Eteghad S, Farhangi MA. Vitamin D administration, cognitive function, BBB permeability and neuroinflammatory factors in high-fat diet-induced obese rats. Int J Obes (Lond) 2017; 41(4):639-44.
16. Nameni G, Hajiluian G, Shahabi P, Farhangi MA, Mesgari-Abbasi M, Hemmati MR. The impact of vitamin D supplementation on neurodegeneration, TNF-α concentration in hypothalamus, and CSF-to-plasma ratio of insulin in high-fat-diet-induced obese rats. J Mol Neurosci 2016; 61(2):247-55.
17. Nameni G, Farhangi MA, Hajilouian G, Shahabi P, Mesgari-Abbasi M. Insulin deficiency: A possible link between obesity and cognitive function. Int J Dev Neurosci 2017; 59(15-20).
18. Liang W, L. Menke A, Driessen A, H. Koek G, H. et al. Establishment of a General NAFLD Scoring System for Rodent Models and Comparison to Human Liver Pathology. PLOS ONE 2014; 9(12):e115922.
19. Shojaei Zarghani S, Soraya H, Zarei L, Alizadeh M. Comparison of Three Different Diet-Induced Non Alcoholic Fatty Liver Disease Protocols in Rats: A Pilot Study. Pharmaceutical Sciences 2016; 22(9-15).
20. Abdelkader NA, Sabry D, Al-Ghussein MAS, Dabbous HM, Allam E. Correlation between vitamin D receptor and monocyte chemotactic protein-1 polymorphisms and spontaneous bacterial peritonitis in decompensated liver disease. JGHR 2015; 4(10):1815-20.
21. Wang YC, Hsieh CC, Kuo HF, Tsai MK, Yang SN, Kuo CH, et al. Effect of vitamin D3 on monocyte chemoattractant protein 1 production in monocytes and macrophages. Acta Cardiol Sin 2014; 30(2):144-50.
22. Ning C, Liu N, Lv Y G, Yang, Zhang Y, Yu R, et al. Lipid metabolism and inflammation modulated by Vitamin D in liver of diabetic rats. Lipids Health Dis 2015; 14:31
23. He G, Karin M. NF-κB and STAT3 – key players in liver inflammation and cancer. Cell Res 2011; 21(1):159–68.
24. Sun B, Karin M. NF-κB signaling, liver disease, and hepatoprotective agents. Oncogene 2008; 27(48):6228–44.
25. Beilfuss A, Sowa JP, Sydor S, Beste M, Bechmann LP, Schlattjan M, et al. Vitamin D counteracts fibrogenic TGF-β signaling in human hepatic stellate cells both receptor-dependently and independently. Gut 2015; 64(5):791-9.
26. Chen J, Katz LH, Muñoz NM, Gu S, Shin J, Jogunoori WS, et al. Vitamin D deficiency promotes liver tumor growth in transforming growth factor-β/Smad3-deficient mice through Wnt and Toll-like receptor 7 pathway modulation. Sci Rep 2016; 6:30217.
27. Nobili V, Giorgio V, Liccardo D, Bedogni G, Morino G, Alisi A, et al. Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol 2014; 170(4):547-53.
28. Lucaci C, Acalovschi M. The importance of vitamin D status in liver histological progression and response to antiviral therapy. HVM Bioflux 2015; 7(3):140-3.
29. Farhangi MA, Keshavarz SA, Eshraghian M, Ostadrahimi A, Saboor-Yaraghi AA. White blood cell count in women: relation to inflammatory biomarkers, hematological profiles, visceral adiposity, and other cardiovascular risk factors. J Health Popul Nutr 2013; 31(1):58-64.
30. Buettner R, Schölmerich J, Bollheimer LC. High‐fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity 2007; 15(4):798-808.
31. McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D 3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J 2008; 7(1):4.
32. Asemi Z, Hashemi T, Karamali M, Samimi M, Esmaillzadeh A. Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial. Am J Clinical Nutr 2013; 98(6):1425-32.
Published
2019-08-17
How to Cite
1.
Yaghchiyan M, Roshangar L, Farhangi M, Mesgari-Abbasi M, Rafiei L, Shahabi P. Histologic, Metabolic, and Inflammatory Changes in the Liver of High-fat Diet-induced Obese Rats before and after Vitamin D Administration. Iran J Allergy Asthma Immunol. 18(4):402-411.
Section
Original Article(s)