Structural Changes to Immune Organs in Rats after Intermittent Fasting Following a High Carb and Fat Diet


Intermittent fasting, thymus, spleen, leukocytes, high carbohydrate diet, high fat diet.

How to Cite

Ika Fidianingsih, Titis Nurmasitoh, Aulia Dian Ashari, DesiYana , & Dwi Nur Ahsani. (2018). Structural Changes to Immune Organs in Rats after Intermittent Fasting Following a High Carb and Fat Diet . Journal of Pharmacy and Nutrition Sciences, 8(1), 6–12.


Background:A diet high in carbs and fat puts people at risk of obesity. Obesity causes changes in the immune system and increases the risk of premature ageing, including in the lymphoid organs ― such as the thymus and spleen. Fasting is expected to improve the immune system. The purpose of this research is to determine the effects of intermittent fasting on images of the structure of the thymus, the number of fat cells, Hassall’s corpuscles of the thymus, the area and density of pulp white spleen, and the number of leukocytes in Wistar rats (Rattus norvegicus) fed a diet high in carbs and fat.

Methods:An experimental study with post-test only control group design, with 15 male rat subjects aged 2.5 months were divided into three groups: first group had a diet that was ad libitum (AL); second group were given a diet high in fats and carbohydrates for 1 month then were fed ad libitum (HCL); and third group were given a diet high in fat and carbohydrates for 1 month continued with alternating 12 hour fasting periods for 72 days (F). Results: Total Hassall’s corpuscles of AL, HCL, and F groups were 1.33 ± 077; 2.58 ± 1.35; and 0.69 ± 0.27, respectively(p = 0.008). Fat cells were not found in the thymus. The largest white pulp in the spleen was found in group F, followed by AL, while the smallest was found in group of HCL (p = 0.01). The most depleted white pulp density was the HCL group. There is no significant difference in the number of leukocytes and different leukocyte count between the groups (p> 0.05).

Conclusion: Intermittent fasting for 72 days affects the number of Hassall’s corpuscles in the thymus and the width of white pulp in the spleen of Wistar rats.


Klenk J, Rapp K, Ulmer H, Concin H, Nagel G. Changes of Body Mass Index in Relation to Mortality: Results of a Cohort of 42,099 Adults. PLOS ONE 2014; 9: e84817.

Flegal KM, Graubard BI, Williamson DF, Gail MH. Cause-Specific Excess Deaths Associated With Underweight, Overweight, and Obesity. JAMA 2007; 298: 2028-37.

Dixit VD. Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span. J Leukoc Biol 2008; 84: 882-92.

Ünalacak M, Kara ?H, Baltaci D, Erdem Ö, Bucaktepe PGE. Effects of Ramadan Fasting on Biochemical and Hema-tological Parameters and Cytokines in Healthy and Obese Individuals. Metab Syndr Relat Disord 2011; 9: 157-61.

Bastani A, Azadmanesh F, Ghorishi SM, Abdoljabary M, Bahrami Z, Heidari MH. Assessment of Malondialdehyde, 8-iso prostaglandin F2?, 8-hydroxy-2'- deoxyguanosine Factors and Protein Carbonyl Groups as Markers of Oxidative Stress in the Fasting Individuals in Tehran. J Appl Environ Biol Sci 2013; 3: 37-41.

Lahdimawan A, Handono K, Indra MR, Prawiro SR. Effect of Ramadan fasting on endorphin and endocannabinoid level in serum, PBMC and macrophage. Int J Pharm Sci Invent 2013; 2: 46-54.

Uno M, Honjoh S, Matsuda M, Hoshikawa H, Kishimoto S, Yamamoto T, et al. A Fasting-Responsive Signaling Pathway that Extends Life Span in C. elegans. Cell Rep 2013; 3: 79-91.

Murphy K, Travers P, Walport M. Janeway’s Immunobiology. 7th ed. Garland Science 2008.

Elmore SA. Enhanced Histopathology of the Immune System: A Review and Update. Toxicol Pathol 2012; 40: 148-56.

Gartner LP, Hiatt, JL. Color Atlas and Text of Histology. 6th ed. Lippincott Williams & Wilkins. 2014

Cesta MF. Normal Structure, Function, and Histology of the Spleen. Toxicol Pathol 2006; 34: 455-65.

Wang J, Vanegas SM, Du X, Noble T, Zingg J-MA, Meydani M, et al. Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit. Nutr Metab 2013; 10: 29.

Nilsson G, Hedberg P, Öhrvik J. White Blood Cell Count in Elderly Is Clinically Useful in Predicting Long-Term Survival. J Aging Res 2014; 2014: 1-6.

Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med 2013; 35: 121.

Yang H, Youm Y-H, Vandanmagsar B, Rood J, Kumar KG, Butler AA, et al. Obesity accelerates thymic aging. Blood 2009; 114: 3803.

Yang H, Youm Y-H, Dixit VD. Inhibition of Thymic Adipogenesis by Caloric Restriction Is Coupled with Reduction in Age-Related Thymic Involution. J Immunol 2009; 183: 3040-52.

Altunkaynak BZ, Ozbek E, Altunkaynak ME. A stereological and histological analysis of spleen on obese female rats, fed with high fat diet. Saudi Med J 2007; 28: 353-357.

Gotoh K, Inoue M, Masaki T, Chiba S, Shimasaki T, Ando H, et al. A novel anti-inflammatory role for spleen-derived interleukin?10 in obesity-induced hypothalamic inflammation. J Neurochem 2012; 120: 752-64.

da Silva AM, Corrêa CL, Neves RH, Machado-Silva JR. A high-fat diet associated with acute schistosomiasis mansoni causes disorganization in splenic architecture in mice. Exp Parasitol 2012; 132: 193-9.

Wu B, Cui H, Peng X, Fang J, Cui W, Liu X. Pathology of spleen in chickens fed on a diet deficient in methionine. Health (N Y) 2012; 04: 32-8.

Siadat Z, Rastin M, Tabasi N, Rezaee A, Mahmoudi M. Evaluation of the Effects of Ramadan Fasting on Lymphocyte subpopulations in a Two?year Follow?up. J Fasting Health 2014; 2(1): 31-6.

Walford RL, Harris SB, Gunion MW. The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc Natl Acad Sci 1992; 89: 11533-11537.

Latifynia A, Vojgani M, Gharagozlou MJ, Sharifian R. Neutrophil function (innate immunity) during Ramadan. J Ayub Med Coll Abbottabad 2009; 21(4): 111-5.

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Copyright (c) 2018 Ika Fidianingsih , Titis Nurmasitoh , Aulia Dian Ashari , Desi Yana  , Dwi Nur Ahsani