Dose-dependent effects of cholecalciferol supplementation on hepatocyte ballooning in Sprague–Dawley rats

Dea Anenta Veonika

doi:10.70347/svsthya.v2i6.134

Authors

Dea Anenta Veonika Department of Nutrition, Faculty of Medicine and Health Sciences, Universitas Jambi https://orcid.org/0000-0002-9687-7899

DOI:

https://doi.org/10.70347/svsthya.v2i6.134

Keywords:

Cholecalciferol, nonalcoholic fatty liver disease, obesity, diet, high-fat, hepatocytes, Sprague–Dawley

Abstract

Obesity is an accumulation of fat body condition due to calories and energy imbalance. Low vitamin D levels are also associated with lower HDL levels, increased triglyceride levels, and increased triglyceride deposition levels in hepatocytes and liver parenchyma. Vitamin D supplementation has various benefits for obesity, such as by improving lipid profiles, reducing BMI, reducing waist circumference, and reducing hip circumference. This study aims to analyze the histopathological changes in the liver of male rats induced by a high-fat, high-fructose diet and supplemented with cholecalciferol. Thirty male Sprague-Dawley rats aged 6-8 weeks were randomly allocated into 5 groups. The normal control (KN) group only received the BR-2 pellet and PAM ad libitum. The negative control (K-) group received a high-fat, high-fructose diet (HFHF) for 28 days. The P1 group received only HFHS for the first 28 days and was supplemented with cholecalciferol 2500 IU thereafter. The P2 group received only HFHF for the first 28 days and was supplemented with cholecalciferol 5000 IU thereafter. The P3 group received only HFHF for the first 28 days and was supplemented with cholecalciferol 10000 IU thereafter. Histopathological analysis involves analyzing the microscopic image of the liver tissue of the obese rat models after receiving treatment with cholecalciferol for 56 days. After 8 weeks of intervention, cholecalciferol supplementation resulted in different findings on histopathological analysis. After intervention with cholecalciferol, there is no significant difference in the degree of steatosis and lobular inflammation on rat liver histopathology (p>0.05). Cholecalciferol supplementation resulted in a significant difference in hepatocyte ballooning on liver histopathology (p<0.05). Administration of cholecalciferol at doses of 2,500 IU, 5,000 IU, and 10,000 IU was not significant in improving liver steatosis and lobular inflammation, but could reduce the occurrence of liver ballooning

Downloads

Download data is not yet available.

Author Biography

Dea Anenta Veonika, Department of Nutrition, Faculty of Medicine and Health Sciences, Universitas Jambi

Department of Nutrition, Faculty of Medicine and Health Sciences, Universitas Jambi

References

Lim Y, Haq N, Boster J. Obesity and comorbid conditions. q. Netherlands: StatPearls Publishing LLC; 2025.

Thamrin SA, Arsyad DS, Kuswanto H, Lawi A, Arundhana AI. Obesity risk-factor variation based on island clusters: A secondary analysis of Indonesian basic health research 2018. Nutrients 2022;14:971. https://doi.org/10.3390/nu14050971.

Lin X, Li H. Obesity: epidemiology, pathophysiology, and therapeutics. Front Endocrinol (Lausanne) 2021;12:706978. https://doi.org/10.3389/fendo.2021.706978.

Visaria A, Setoguchi S. Body mass index and all-cause mortality in a 21st century U.S. population: A national health interview survey analysis. PLoS One 2023;18:e0287218. https://doi.org/10.1371/journal.pone.0287218.

Masood B, Moorthy M. Causes of obesity: a review. Clin Med 2023;23:284–91. https://doi.org/10.7861/clinmed.2023-0168.

Karampela I, Sakelliou A, Vallianou N, Christodoulatos G-S, Magkos F, Dalamaga M. Vitamin D and obesity: current evidence and controversies. Curr Obes Rep 2021;10:162–80. https://doi.org/10.1007/s13679-021-00433-1.

Aldana A, Aljaroudi W, Estes C, Rizvi F, Okeke-Moffatt C, Minakova V. Childhood obesity and its correlation with vitamin D: A systematic review. Cureus 2025;17:e85047. https://doi.org/10.7759/cureus.85047.

Park CY, Han SN. Vitamin D and obesity. Adv Food Nutr Res 2024;109:221–47. https://doi.org/10.1016/bs.afnr.2023.12.006.

Gholamzad A, Khakpour N, Kabipour T, Gholamzad M. Association between serum vitamin D levels and lipid profiles: a cross-sectional analysis. Sci Rep 2023;13:21058. https://doi.org/10.1038/s41598-023-47872-5.

Frențușcă C, Babeș K. Association between vitamin D deficiency and serum lipid levels in a group of Romanian patients. Med Pharm Rep 2024;97:263–9. https://doi.org/10.15386/mpr-2714.

Kumar M, Parchani A, Kant R, Das A. Relationship between vitamin D deficiency and non-alcoholic fatty liver disease: A cross-sectional study from a tertiary care center in Northern India. Cureus 2023:e34921. https://doi.org/10.7759/cureus.34921.

Gerveieeha Z, Siassi F, Qorbani M, Menbar RS, Ahmadi MH, Sotoudeh G. The effect of vitamin D supplementation on body composition in nursing mothers with overweight or obesity: a randomized double-blind placebo-controlled clinical trial. BMC Nutr 2023;9:1. https://doi.org/10.1186/s40795-022-00664-y.

Cordeiro A, Pereira SE, Saboya CJ, Ramalho A. Vitamin D Supplementation and Its relationship with loss of visceral adiposity. Obes Surg 2022;32:3419–25. https://doi.org/10.1007/s11695-022-06239-x.

Rahimi S, Angaji SA, Majd A, Hatami B, Baghaei K. A fast and accurate mouse model for inducing non-alcoholic steatohepatitis. Gastroenterol Hepatol Bed Bench 2022;15:406–14. https://doi.org/10.22037/ghfbb.v15i4.2593.

Adnyana IMDM. Desain Penelitian Kuantitatif. In: Akbar H, editor. Metodologi Penelitian. 1st ed., Bandung: CV. Media Sains Indonesia; 2024, p. 45–68.

Sukmawati AS, Hermawan IMA, Saputra EK, Adnyana IMDM, Aldyza N, Slamet NS, Hidayat B, Pandawa RM, Hamdani R, Maisura, Dara W, Sembodo A. Metodologi Penelitian. 1st ed. Bandung: CV. Media Sains Indonesia; 2024.

Leow W-Q, Chan AW-H, Mendoza PGL, Lo R, Yap K, Kim H. Non-alcoholic fatty liver disease: the pathologist’s perspective. Clin Mol Hepatol 2023;29:S302–18. https://doi.org/10.3350/cmh.2022.0329.

Aboujassoum HM, Mohamed-Ali V, Abraham D, Clapp LH, Al-Naemi HA. Relative recovery of non-alcoholic fatty liver disease (NAFLD) in diet-induced obese rats. Nutrients 2023;16:115. https://doi.org/10.3390/nu16010115.

Maciejewska D, Łukomska A, Dec K, Skonieczna-Żydecka K, Gutowska I, Skórka-Majewicz M, Styburski D, Misiakiewicz-Has K, Pilutin A, Palma J, Sieletycka K, Marlicz W, Stachowska E. Diet-induced rat model of gradual development of non-alcoholic fatty liver disease (NAFLD) with lipopolysaccharides (LPS) secretion. Diagnostics 2019;9:205. https://doi.org/10.3390/diagnostics9040205.

de Moura e Dias M, dos Reis SA, da Conceição LL, Sediyama CMN de O, Pereira SS, de Oliveira LL, Gouveia Peluzio M do C, Martinez JA, Milagro FI. Diet-induced obesity in animal models: points to consider and influence on metabolic markers. Diabetol Metab Syndr 2021;13:32. https://doi.org/10.1186/s13098-021-00647-2.

Du T, Xiang L, Zhang J, Yang C, Zhao W, Li J, Zhou Y, Ma L. Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation. Front Endocrinol (Lausanne) 2023;14:e1138078. https://doi.org/10.3389/fendo.2023.1138078.

Emam RF, Soliman AF, Darweesh SK, AbdElmagid RA, Ibrahim OM, Mohamed DM. Steatosis regression assessed by cap after Vitamin ‘D’ supplementation in NAFLD patients with Vitamin ‘D’ deficiency. Eur J Gastroenterol Hepatol 2024;36:101–6. https://doi.org/10.1097/MEG.0000000000002653.

Liu M, Song X-Z, Yang L, Fang Y-H, Lan L, Cui J-S, Lu X-C, Zhu H-Y, Quan L-H, Han H-M. 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model. Front Endocrinol 2025;16:1528768. https://doi.org/10.3389/fendo.2025.1528768.

El Amrousy D, Abdelhai D, Shawky D. Vitamin D and nonalcoholic fatty liver disease in children: a randomized controlled clinical trial. Eur J Pediatr 2022;181:579–86. https://doi.org/10.1007/s00431-021-04243-4.

Hu L, Velu P, Prabahar K, Hernández-Wolters B, Kord-Varkaneh H, Xu Y. Effect of vitamin D supplementation on lipid profile in overweight or obese women: A meta-analysis and systematic review of randomized controlled trials. Nutr Rev 2025;83:1657–68. https://doi.org/10.1093/nutrit/nuae226.

Ge L, Gao S, Kia N, Wang Y, Hua L. Effect of vitamin D supplementation on body composition, lipid profile, and glycemic indices in patients with obesity-associated metabolic syndrome: a systematic review and meta-analysis. Diabetol Metab Syndr 2025;17:287. https://doi.org/10.1186/s13098-025-01799-1.

Li Y, Zheng T, Xiao S, Wang P, Yang W, Jiang L, Chen L, Sha J, Jin Y, Chen S, Byrne CD, Targher G, Li J, Zheng M. Hepatocytic ballooning in non‐alcoholic steatohepatitis: Dilemmas and future directions. Liver International 2023;43:1170–82. https://doi.org/10.1111/liv.15571.

Ajoolabady A, Kaplowitz N, Lebeaupin C, Kroemer G, Kaufman RJ, Malhi H, Ren J. Endoplasmic reticulum stress in liver diseases. Hepatology 2023;77:619–39. https://doi.org/10.1002/hep.32562.

Dal K, Uzman M, Ata N, Ertugrul DT, Bursa N, Caglayan M, Baser S, Akkan T, Imrat E, Celik O, Ulgu MM, Sahin M, Birinci S. The effect of vitamin D status on non-alcoholic fatty liver disease: a population-based observational study. Endokrynol Pol 2023;74:63–6. https://doi.org/10.5603/EP.a2023.0002.

Yilmaz Y. Review article: non‐alcoholic fatty liver disease and osteoporosis – clinical and molecular crosstalk. Aliment Pharmacol Ther 2012;36:345–52. https://doi.org/10.1111/j.1365-2036.2012.05196.x.

Martinekova P, Obeidat M, Topala M, Váncsa S, Veres DS, Zolcsák Á, Pál M, Földvári-Nagy L, Banovcin P, Erőss B, Hegyi P, Hagymasi K. Role of vitamin D supplementation in chronic liver disease: A systematic review and meta-analysis of randomized controlled trials. Nutr Rev 2025;83:2043–54. https://doi.org/10.1093/nutrit/nuaf117.

Zhang X-L, Chen L, Yang J, Zhao S-S, Jin S, Ao N, Yang J, Liu H-X, Du J. Vitamin D alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism. Front Microbiol 2023;14:e1117644. https://doi.org/10.3389/fmicb.2023.1117644.

Adnyana IMDM. Educational video module for increasing treatment rates for alcohol use disorders in inpatients. World J Hepatol 2026;18:115013. https://doi.org/10.4254/wjh.v18.i1.115013.

Wierzbicka A, Oczkowicz M. Sex differences in vitamin D metabolism, serum levels and action. British Journal of Nutrition 2022;128:2115–30. https://doi.org/10.1017/S0007114522000149.

Antunes C, Azadfard M, Hoilat GJ, Gupta M. Fatty Liver. New York, Treasure Island (FL): 2025.