Authors :
Srijana M Shekar; Ravindra P V; Asna Urooj
Volume/Issue :
Volume 10 - 2025, Issue 8 - August
Google Scholar :
https://tinyurl.com/3tuf4jsj
Scribd :
https://tinyurl.com/uvamtvrn
DOI :
https://doi.org/10.38124/ijisrt/25aug156
Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.
Note : Google Scholar may take 30 to 40 days to display the article.
Abstract :
Calorie restriction, the nutritional intervention which reduces calorie intake without incurring malnutrition has
been reported to reduce inflammation and the expression of inflammatory genes. Diabetes is associated with low grade
inflammation state. The effect of calorie restriction on the expression of apoptosis and inflammatory genes in male Wistar
rats induced with diabetes was investigated and compared with the control group. The lung cells were harvested, isolated,
incubated and observed for the formation of epithelial and/or fibroblast monolayer. The extracted total RNA was reverse
transcribed into cDNA, and real-time PCR was carried out. The alveolar cells were cultured in growth media simulating
calorie restriction and hyperglycemia and were observed for phenotypic changes and gene expression. Changes in
morphology were observed in cells cultured in high glucose, resembling fibroblast phenotype, 10 days post culture. The
expression levels of apoptotic genes such as bax, TNF-α, caspase 3 and caspase 8 and pro-inflammatory genes such as
Rantes, iNOS, MCP-1, MIP-2 and IL-1 were substantially up regulated in the diabetes induced alveolar epithelial cells
compared to that of non-diabetes induced alveolar epithelial cells suggesting that diabetes induced pathological changes in
the lung were associated with the induction of apoptosis and inflammation. Overall, this study provides evidence that a
planned calorie restriction in diabetes significantly down-regulates the expression levels of inflammatory and apoptotic
genes, which is likely to improving metabolic outcomes in type 2 diabetes.
Keywords :
Calorie Restriction, Diabetes, Apoptotic and Inflammatory Genes.
References :
- Larson-Meyer, D. E., Redman, L., Heilbronn, L. K., Martin, C. K., & Ravussin, E. (2010). Caloric restriction with or without exercise: The fitness versus fatness debate. Medicine & Science in Sports & Exercise, 42(1), 152–159.
- Lefevre, M., Redman, L. M., Heilbronn, L. K., Smith, J. V., Martin, C. K., Rood, J. C., Greenway, F. L., Williamson, D. A., Smith, S. R., & Ravussin, E. (2009). Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis, 203(1), 206–213. https://doi.org/10.1016/j.atherosclerosis.2008.06.026
- Hung, Y.-H., Linden, M. A., Gordon, A., Rector, R. S., & Buhman, K. K. (2015). Endurance exercise training programs intestinal lipid metabolism in a rat model of obesity and type 2 diabetes. Physiological Reports, 3(1), e12232. https://doi.org/10.14814/phy2.12232
- Kitada, M., Takeda, A., Nagai, T., Ito, H., Kanasaki, K., & Koya, D. (2011). Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa/fa) rats: A model of type 2 diabetes. Experimental Diabetes Research, 2011, 1–11. https://doi.org/10.1155/2011/908185
- Omodei, D., & Fontana, L. (2011). Calorie restriction and prevention of age-associated chronic disease. FEBS Letters, 585(11), 1537–1542. https://doi.org/10.1016/j.febslet.2011.04.010
- Navarro-González, J. F., Mora-Fernández, C., De Fuentes, M. M., & García-Pérez, J. (2011). Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nature Reviews Nephrology, 7(6), 327–340. https://doi.org/10.1038/nrneph.2011.51
- Ye, J., & Keller, J. N. (2010). Regulation of energy metabolism by inflammation: A feedback response in obesity and calorie restriction. Aging (Albany NY), 2(6), 361–368. https://doi.org/10.18632/aging.100162
- Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., & Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201–204. https://doi.org/10.1126/science.1173635
- International Diabetes Federation. (n.d.). Diabetes facts & figures. https://idf.org/about-diabetes/diabetes-facts-figures/
- Nicklas, B. J., Wang, X., You, T., Lyles, M. F., Demons, J., Easter, L., Berry, M. J., Lenchik, L., & Carr, J. J. (2009). Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: A randomized, controlled trial. The American Journal of Clinical Nutrition, 89(4), 1043–1052. https://doi.org/10.3945/ajcn.2008.27091
- Chung, H. Y., Sung, B., Jung, K. J., Zou, Y., & Yu, B. P. (2006). The molecular inflammatory process in aging. Antioxidants & Redox Signaling, 8(3–4), 572–581. https://doi.org/10.1089/ars.2006.8.572
- Fontana, L. (2008). Calorie restriction and cardiometabolic health. European Journal of Cardiovascular Prevention & Rehabilitation, 15(1), 3–9. https://doi.org/10.1097/HJR.0b013e3282f2b5d7
- Fontana, L., Partridge, L., & Longo, V. D. (2010). Extending healthy life span—from yeast to humans. Science, 328(5976), 321–326. https://doi.org/10.1126/science.1172539
- Fontana, L., Meyer, T. E., Klein, S., & Holloszy, J. O. (2004). Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences of the United States of America, 101(17), 6659–6663. https://doi.org/10.1073/pnas.0308291101
- Williams, T. D., Chambers, J. B., Henderson, R. P., Rashotte, M. E., & Overton, J. M. (2002). Cardiovascular responses to caloric restriction and thermoneutrality in C57BL/6J mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 282(6), R1459–R1467. https://doi.org/10.1152/ajpregu.00640.2001
- Atalay, B., Dogan, S., Gudu, B. O., Yilmaz, E., Ayden, A., Ozorhan, U., Cicekdal, M. B., Yaltirik, K., Ekici, I. D., & Tuna, B. G. (2024). Neurodegeneration: Effects of calorie restriction on the brain sirtuin protein levels. Behavioural Brain Research, 476, 115258. https://doi.org/10.1016/j.bbr.2024.115258
- Jantsch, J., da Silva Rodrigues, F., Silva Dias, V., de Farias Fraga, G., Eller, S., Giovenardi, M., & Guedes, R. P. (2024). Calorie restriction attenuates memory impairment and reduces neuroinflammation in obese aged rats. Molecular Neurobiology, 62(2), 1788–1799. https://doi.org/10.1007/s12035-024-04360-9
- Yu, Q., Zou, L., Kong, Z., & Yang, L. (2020). Cognitive impact of calorie restriction: A narrative review. Journal of the American Medical Directors Association, 21(10), 1394–1401. https://doi.org/10.1016/j.jamda.2020.05.047
- Liu, Y., Chen, Y., Ma, J., Lin, J., Liu, C., Li, X., Xu, Y., Kuang, H., Shi, L., Xue, Y., Feng, B., Zhu, D., Wang, G., Yang, J., Xiao, X., Yu, X., Zhou, J., Bao, Y., Su, Q., … Li, X. (2025). Dapagliflozin plus calorie restriction for remission of type 2 diabetes: Multicentre, double-blind, randomised, placebo-controlled trial. BMJ, 381, e078917. https://doi.org/10.1136/bmj-2024-078917
- Sun, X., Li, F., Yan, H., Chang, X., Yao, X., Yang, X., Wu, S., Suo, Y., Zhu, X., Wang, C., Gao, J., Wang, H., Chen, Y., Xia, M., Bian, H., & Gao, X. (2024). Intermittent compared with continuous calorie restriction for treatment of metabolic dysfunction-associated steatotic liver disease: A randomized clinical trial. The American Journal of Clinical Nutrition. Advance online publication. https://doi.org/10.1016/j.ajcnut.2024.10.012
- Nikitchenko, Y. V., Klochkov, V. K., Kavok, N. S., Karpenko, N. A., Yefimova, S. L., Semynozhenko, V. P., Nikitchenko, I. V., & Bozhkov, A. I. (2024). Geroprotective effects of GdVO₄:Eu³⁺ nanoparticles, metformin and calorie restriction in male rats with accelerated aging induced by overnutrition in early postnatal ontogenesis. Biogerontology, 26(1). https://doi.org/10.1007/s10522-024-10156-0
- Viskupicová, J., Blaškovič, D., Galiniak, S., Soszyński, M., Bartosz, G., Horáková, L., & Sadowska-Bartosz, I. (2015). Effect of high glucose concentrations on human erythrocytes in vitro. Redox Biology, 5, 381–387. https://doi.org/10.1016/j.redox.2015.06.015
- Usuki, J., Enomoto, T., Azuma, A., Matsuda, K., Aoyama, A., & Kudoh, S. (2001). Influence of hyperglycemia on the severity of pulmonary fibrosis. Chest, 120(1_suppl), S71. https://doi.org/10.1378/chest.120.1_suppl.S71
- Fiorentino, T. V., Prioletta, A., Zuo, P., & Folli, F. (2013). Hyperglycemia-induced oxidative stress and its role in diabetes mellitus–related cardiovascular diseases. Current Pharmaceutical Design, 19(32), 5695–5703. https://doi.org/10.2174/13816128113199990338
- Chung, H. Y., Lee, E. K., Choi, Y. J., Kim, J. M., Kim, D. H., Zou, Y., & Jung, J. H. (2011). Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. Journal of Dental Research, 90(7), 830–840. https://doi.org/10.1177/0022034510384142
Calorie restriction, the nutritional intervention which reduces calorie intake without incurring malnutrition has
been reported to reduce inflammation and the expression of inflammatory genes. Diabetes is associated with low grade
inflammation state. The effect of calorie restriction on the expression of apoptosis and inflammatory genes in male Wistar
rats induced with diabetes was investigated and compared with the control group. The lung cells were harvested, isolated,
incubated and observed for the formation of epithelial and/or fibroblast monolayer. The extracted total RNA was reverse
transcribed into cDNA, and real-time PCR was carried out. The alveolar cells were cultured in growth media simulating
calorie restriction and hyperglycemia and were observed for phenotypic changes and gene expression. Changes in
morphology were observed in cells cultured in high glucose, resembling fibroblast phenotype, 10 days post culture. The
expression levels of apoptotic genes such as bax, TNF-α, caspase 3 and caspase 8 and pro-inflammatory genes such as
Rantes, iNOS, MCP-1, MIP-2 and IL-1 were substantially up regulated in the diabetes induced alveolar epithelial cells
compared to that of non-diabetes induced alveolar epithelial cells suggesting that diabetes induced pathological changes in
the lung were associated with the induction of apoptosis and inflammation. Overall, this study provides evidence that a
planned calorie restriction in diabetes significantly down-regulates the expression levels of inflammatory and apoptotic
genes, which is likely to improving metabolic outcomes in type 2 diabetes.
Keywords :
Calorie Restriction, Diabetes, Apoptotic and Inflammatory Genes.