Sodium Acetate Attenuates Fructose-Induced Mitochondrial Dysfunction and Cardiometabolic Disorders in Pregnant Wistar Rats
DOI :
https://doi.org/10.54548/njps.v40i2.15Résumé
Cardiometabolic disorder is a leading cause of mortality, and mitochondrial dysfunction plays a significant role in its pathophysiology. The mechanisms by which acetate improves fructose-induced cardiometabolic disturbances in pregnancy remain unclear. This study aimed at investigating the role of acetate in modulating the fructose-induced cardiometabolic risks in pregnancy. Thirty-six female Wistar rats (120-150g) were divided into six groups, n=6. A total of 18 rats were made pregnant and 18 non-pregnant. The groups consisted of control (C), fructose (F), and fructose-acetate (FA). The FA group received 10% (w/v) fructose plus sodium acetate (200mg/kg) and distilled water. After three weeks, animals were anesthetized with ketamine (90mg/kg) and xylazine (10mg/kg). Blood and tissue homogenates were analyzed, and data were expressed as mean ± SEM, with significant difference accepted at p < 0.05. Compared to control, fasting blood sugar (FBS), triglyceride-glucose index (TyG), circulatory free fatty acids (FFA), uric acid (UA), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were significantly higher in fructose-treated pregnant rats, and non-pregnant rats. In contrast, high-density lipoprotein-cholesterol (HDL), pyruvate dehydrogenase (PDH), and cardiac aconitase activities were significantly lower in both non-pregnant and pregnant rats, with a more profound effect seen in pregnant rats. Meanwhile, pregnancy significantly exacerbated the fructose-induced alteration in UA, FFA, TG, HDL and MDA. Fructose-induced cardiometabolic alterations were mitigated by acetate irrespective of the gestational status. Acetate restores mitochondrial oxidative capacity in pregnancy, making it a potential therapeutic agent for improving mitochondrial metabolic activities in debilitating gestational cardiac disorders.
Téléchargements
Références
Alberti, K. G. M. M., Zimmet, P., & Shaw, J. (2006). Metabolic syndrome—A new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabetic Medicine: A Journal of the British Diabetic Association, 23(5), 469–480. https://doi.org/10.1111/j.1464-5491.2006.01858.x
AlZaim, I., Eid, A. H., Abd-Elrahman, K. S., & El-Yazbi, A. F. (2022). Adipose tissue mitochondrial dysfunction and cardiometabolic diseases: On the search for novel molecular targets. Biochemical Pharmacology, 206, 115337. https://doi.org/10.1016/j.bcp.2022.115337
Annandale, M., Daniels, L. J., Li, X., Neale, J. P. H., Chau, A. H. L., Ambalawanar, H. A., James, S. L., Koutsifeli, P., Delbridge, L. M. D., & Mellor, K. M. (2021). Fructose Metabolism and Cardiac Metabolic Stress. Frontiers in Pharmacology, 12, 695486. https://doi.org/10.3389/fphar.2021.695486
Chan, A. M. L., Ng, A. M. H., Mohd Yunus, M. H., Idrus, R. B. H., Law, J. X., Yazid, M. D., Chin, K.-Y., Shamsuddin, S. A., & Lokanathan, Y. (2021). Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review. Nutrients, 13(8), 2497. https://doi.org/10.3390/nu13082497
Chandel, N. S. (2021). Mitochondria. Cold Spring Harbor Perspectives in Biology, 13(3), a040543. https://doi.org/10.1101/cshperspect.a040543
Colmenares-Mejia, C. C., Quintero-Lesmes, D. C., Bautista-Niño, P. K., Guío, E., Paez, M. C., Beltrán, M., Williams, D., Gray, K. J., Casas, J. P., & Serrano, N. C. (2023). Uric acid and risk of pre-eclampsia: Results from a large case-control study and meta-analysis of prospective studies. Scientific Reports, 13(1), 3018. https://doi.org/10.1038/s41598-023-29651-4
Dai, D.-F., Johnson, S. C., Villarin, J. J., Chin, M. T., Nieves-Cintrón, M., Chen, T., Marcinek, D. J., Dorn, G. W., Kang, Y. J., Prolla, T. A., Santana, L. F., & Rabinovitch, P. S. (2011). Mitochondrial Oxidative Stress Mediates Angiotensin II–Induced Cardiac Hypertrophy and Gαq Overexpression–Induced Heart Failure. Circulation Research, 108(7), 837–846. https://doi.org/10.1161/CIRCRESAHA.110.232306
Dikalov, S. I., & Ungvari, Z. (2013). Role of mitochondrial oxidative stress in hypertension. American Journal of Physiology - Heart and Circulatory Physiology, 305(10), H1417–H1427. https://doi.org/10.1152/ajpheart.00089.2013
Glantzounis, G. K., Tsimoyiannis, E. C., Kappas, A. M., & Galaris, D. A. (2005). Uric acid and oxidative stress. Current Pharmaceutical Design, 11(32), 4145–4151. https://doi.org/10.2174/138161205774913255
Guo, Y., Lu, J., Bahani, M., Ding, G., Wang, L., Zhang, Y., Zhang, H., Liu, C., Zhou, L., Liu, X., Li, F., Wang, X., & Ding, H. (2024). Triglyceride-glucose index in early pregnancy predicts the risk of gestational diabetes: A prospective cohort study. Lipids in Health and Disease, 23(1), 87. https://doi.org/10.1186/s12944-024-02076-2
Haddad-Tóvolli, R., & Claret, M. (2023). Metabolic and feeding adjustments during pregnancy. Nature Reviews Endocrinology, 19(10), 564–580. https://doi.org/10.1038/s41574-023-00871-y
Hadden, D. R., & McLaughlin, C. (2009). Normal and abnormal maternal metabolism during pregnancy. Seminars in Fetal & Neonatal Medicine, 14(2), 66–71. https://doi.org/10.1016/j.siny.2008.09.004
Han, Y., Zhou, Z., Zhang, Y., Zhao, G., & Xu, B. (2023). The Association of Surrogates of Insulin Resistance with Hyperuricemia among Middle-Aged and Older Individuals: A Population-Based Nationwide Cohort Study. Nutrients, 15(14), 3139. https://doi.org/10.3390/nu15143139
Hannou, S. A., Haslam, D. E., McKeown, N. M., & Herman, M. A. (2018). Fructose metabolism and metabolic disease. The Journal of Clinical Investigation, 128(2), 545–555. https://doi.org/10.1172/JCI96702
Hsu, C.-N., Yu, H.-R., Chan, J. Y. H., Lee, W.-C., Wu, K. L. H., Hou, C.-Y., Chang-Chien, G.-P., Lin, S., & Tain, Y.-L. (2022). Maternal Acetate Supplementation Reverses Blood Pressure Increase in Male Offspring Induced by Exposure to Minocycline during Pregnancy and Lactation. International Journal of Molecular Sciences, 23(14), 7924. https://doi.org/10.3390/ijms23147924
Hu, S., Kuwabara, R., de Haan, B. J., Smink, A. M., & de Vos, P. (2020). Acetate and Butyrate Improve β-cell Metabolism and Mitochondrial Respiration under Oxidative Stress. International Journal of Molecular Sciences, 21(4), 1542. https://doi.org/10.3390/ijms21041542
Hurd, T. R., Collins, Y., Abakumova, I., Chouchani, E. T., Baranowski, B., Fearnley, I. M., Prime, T. A., Murphy, M. P., & James, A. M. (2012). Inactivation of Pyruvate Dehydrogenase Kinase 2 by Mitochondrial Reactive Oxygen Species. The Journal of Biological Chemistry, 287(42), 35153–35160. https://doi.org/10.1074/jbc.M112.400002
Jahan, F., Vasam, G., Green, A. E., Bainbridge, S. A., & Menzies, K. J. (2023). Placental Mitochondrial Function and Dysfunction in Preeclampsia. International Journal of Molecular Sciences, 24(4), 4177. https://doi.org/10.3390/ijms24044177
Joseph, S., Li, M., Zhang, S., Horne, L., Stacpoole, P. W., Wohlgemuth, S. E., Edison, A. S., Wood, C., & Keller-Wood, M. (2022). Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 322(1), R83–R98. https://doi.org/10.1152/ajpregu.00185.2021
Louwagie, E. J., Larsen, T. D., Wachal, A. L., Gandy, T. C. T., & Baack, M. L. (2021). Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes. International Journal of Molecular Sciences, 22(5), 2382. https://doi.org/10.3390/ijms22052382
Lu, Q., Zhang, J., Xin, L., Lou, Y., Qin, F., Zhao, L., & Xiong, Z. (2023). Integrated gas chromatography-mass spectrometry and ultra-high-performance liquid chromatography-mass spectrometry renal metabolomics and lipidomics deciphered the metabolic regulation mechanism of Gushudan on kidney-yang-deficiency-syndrome rats. Journal of Separation Science, 46(13), e2300124. https://doi.org/10.1002/jssc.202300124
Lüscher, B. P., Schoeberlein, A., Surbek, D. V., & Baumann, M. U. (2022). Hyperuricemia during Pregnancy Leads to a Preeclampsia-Like Phenotype in Mice. Cells, 11(22), 3703. https://doi.org/10.3390/cells11223703
Marín, R., Chiarello, D. I., Abad, C., Rojas, D., Toledo, F., & Sobrevia, L. (2020). Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia. Biochimica Et Biophysica Acta. Molecular Basis of Disease, 1866(12), 165961. https://doi.org/10.1016/j.bbadis.2020.165961
Mustaphi, R., Gopalan, S., Dhaliwal, L., & Sarkar, A. K. (1996). Hyperuricemia and pregnancy induced hypertension—Reappraisal. Indian Journal of Medical Sciences, 50(3), 68–71.
Oyabambi, A. O., Bamidele, O., Aindero, B. B., & Awolola, A. M. (2024). L-arginine mitigates cardiac lipid and glucose accumulation through leptin modulation and enhancement of PIK3 activities in high fat-fed male Wistar rats. Nutrition & Metabolism, 21(1), 103. https://doi.org/10.1186/s12986-024-00852-6
Oyabambi, A. O., Michael, O. S., Areola, E. D., Saliu, S. B., & Olatunji, L. A. (2021). Sodium acetate ameliorated systemic and renal oxidative stress in high-fructose insulin-resistant pregnant Wistar rats. Naunyn-Schmiedeberg’s Archives of Pharmacology, 394(7), 1425–1435. https://doi.org/10.1007/s00210-021-02058-6
Raji, S. R., Nandini, R. J., Ashok, S., Anand, C. R., Vivek, V. P., Jayakumar, K., Harikrishnan, V. S., Manjunatha, S., & Gopala, S. (2021). Diminished substrate-mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats. IUBMB Life, 73(4), 676–689. https://doi.org/10.1002/iub.2449
Ramanathan, R., & Ibdah, J. A. (2022). Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy. International Journal of Molecular Sciences, 23(7), 3595. https://doi.org/10.3390/ijms23073595
Ramlakhan, K. P., Johnson, M. R., & Roos-Hesselink, J. W. (2020). Pregnancy and cardiovascular disease. Nature Reviews. Cardiology, 17(11), 718–731. https://doi.org/10.1038/s41569-020-0390-z
Regnault, T. R., Gentili, S., Sarr, O., Toop, C. R., & Sloboda, D. M. (2013). Fructose, pregnancy and later life impacts. Clinical and Experimental Pharmacology and Physiology, 40(11), 824–837. https://doi.org/10.1111/1440-1681.12162
Riis, J. L., Cook, S. H., Letourneau, N., Campbell, T., Granger, D. A., & Giesbrecht, G. F. (2022). Characterizing and Evaluating Diurnal Salivary Uric Acid Across Pregnancy Among Healthy Women. Frontiers in Endocrinology, 13, 813564. https://doi.org/10.3389/fendo.2022.813564
Russo, B., Menduni, M., Borboni, P., Picconi, F., & Frontoni, S. (2021). Autonomic Nervous System in Obesity and Insulin-Resistance—The Complex Interplay between Leptin and Central Nervous System. International Journal of Molecular Sciences, 22(10), 5187. https://doi.org/10.3390/ijms22105187
Sagy, I., Salman, A. A., Kezerle, L., Erez, O., Yoel, I., & Barski, L. (2017). Peripartum cardiomyopathy is associated with increased uric acid concentrations: A population based study. Heart & Lung: The Journal of Critical Care, 46(5), 369–374. https://doi.org/10.1016/j.hrtlng.2017.06.004
Saklayen, M. G. (2018). The Global Epidemic of the Metabolic Syndrome. Current Hypertension Reports, 20(2), 12. https://doi.org/10.1007/s11906-018-0812-z
Shastry, A., & Dunham-Snary, K. (2023). Metabolomics and mitochondrial dysfunction in cardiometabolic disease. Life Sciences, 333, 122137. https://doi.org/10.1016/j.lfs.2023.122137
Smith, E. V. L., Dyson, R. M., Weth, F. R., Berry, M. J., & Gray, C. (2022). Maternal Fructose Intake, Programmed Mitochondrial Function and Predisposition to Adult Disease. International Journal of Molecular Sciences, 23(20), 12215. https://doi.org/10.3390/ijms232012215
Sobrevia, L., Valero, P., Grismaldo, A., Villalobos-Labra, R., Pardo, F., Subiabre, M., Armstrong, G., Toledo, F., Vega, S., Cornejo, M., Fuentes, G., & Marín, R. (2020). Mitochondrial dysfunction in the fetoplacental unit in gestational diabetes mellitus. Biochimica Et Biophysica Acta. Molecular Basis of Disease, 1866(12), 165948. https://doi.org/10.1016/j.bbadis.2020.165948
Softic, S., Cohen, D. E., & Kahn, C. R. (2016). Role of Dietary Fructose and Hepatic de novo Lipogenesis in Fatty Liver Disease. Digestive Diseases and Sciences, 61(5), 1282–1293. https://doi.org/10.1007/s10620-016-4054-0
Sweeting, A., Wong, J., Murphy, H. R., & Ross, G. P. (2022). A Clinical Update on Gestational Diabetes Mellitus. Endocrine Reviews, 43(5), 763–793. https://doi.org/10.1210/endrev/bnac003
Tappy, L., & Lê, K.-A. (2010). Metabolic effects of fructose and the worldwide increase in obesity. Physiological Reviews, 90(1), 23–46. https://doi.org/10.1152/physrev.00019.2009
Taskinen, M.-R., Packard, C. J., & Borén, J. (2019). Dietary Fructose and the Metabolic Syndrome. Nutrients, 11(9), 1987. https://doi.org/10.3390/nu11091987
Yazıcı, D., & Sezer, H. (2017). Insulin Resistance, Obesity and Lipotoxicity. Advances in Experimental Medicine and Biology, 960, 277–304. https://doi.org/10.1007/978-3-319-48382-5_12
Zhang, M., Cui, R., Zhou, Y., Ma, Y., Jin, Y., Gou, X., Yang, J., & Wu, X. (2023). Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress. Toxicology, 483, 153387. https://doi.org/10.1016/j.tox.2022.153387
Zhang, Q., Xiao, X., Zheng, J., Li, M., Yu, M., Ping, F., Wang, T., & Wang, X. (2018). A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3. BioMed Research International, 2018, 3109251. https://doi.org/10.1155/2018/3109251
Téléchargements
Publié
Numéro
Rubrique
Licence
© Nigerian Journal of Physiological Sciences 2025
Cette œuvre est sous licence Creative Commons Attribution 4.0 International.
