El papel de las acuaporinas en el metabolismo energético y su relación con la resistencia a la insulina
DOI:
https://doi.org/10.57188/Keywords:
Acuaporinas, Aquagliceroporinas, Metabolismo energético, Resistencia a la insulinaAbstract
La resistencia a la insulina es un eje central del síndrome metabólico y de la epidemia creciente de diabetes tipo 2, cuyo desarrollo se asocia a obesidad, sedentarismo y desajustes en la homeostasis glucolipídica. En este contexto, las acuaporinas, en especial las aquagliceroporinas AQP7 y AQP9, han emergido como reguladores críticos del metabolismo energético al facilitar el transporte de glicerol entre tejido adiposo, hígado y otros órganos metabólicamente activos. Esta revisión integra la evidencia reciente sobre la estructura y clasificación de las acuaporinas, su distribución tisular y su participación en los mecanismos moleculares de la resistencia a la insulina, incluyendo inflamación crónica, lipotoxicidad, estrés oxidativo y disfunción mitocondrial. Se describe cómo la desregulación de AQP7 en adipocitos favorece la hipertrofia y el acúmulo de triglicéridos, mientras que las alteraciones de AQP9 condicionan la entrada hepática de glicerol y contribuyen a esteatosis y alteraciones en la gluconeogénesis. Asimismo, se analizan los aportes de otras isoformas como AQP3, AQP8 y AQP11 en la modulación del estado redox y de la señalización insulínica. Finalmente, se abordan las implicaciones terapéuticas de la modulación de aquaporinas mediante intervenciones nutricionales, fármacos y compuestos naturales, resaltando su potencial como biomarcadores y dianas terapéuticas, pero también las limitaciones derivadas del predominio de estudios experimentales y la escasez de datos en poblaciones locales.
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1. Fahed G, Aoun L, Bou Zerdan M, Allam S, Bou Zerdan M, Bouferraa Y, et al. Metabolic syndrome: updates on pathophysiology and management in 2021. Int J Mol Sci. 2022;23(2):786. Doi: 10.3390/ijms23020786
2. Zhao X, An X, Yang C, Sun W, Ji H, Lian F. The crucial role and mechanism of insulin resistance in metabolic disease. Front Endocrinol (Lausanne). 2023;14:1149239. Doi: 10.3389/fendo.2023.1149239
3. Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J. 2022;46(1):15-37. https://doi.org/10.4093/dmj.2021.0280
4. Saini V. Molecular mechanisms of insulin resistance in type 2 diabetes mellitus. World J Diabetes. 2010;1(3):68-75. Doi: 10.4239/wjd.v1.i3.68
5. Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther. 2022;7(1):216. Doi: 10.1038/s41392-022-01073-0
6. Chandrasekaran P, Weiskirchen R. Cellular and molecular mechanisms of insulin resistance. Curr Tissue Microenviron Rep. 2024;5(3):79-90. Doi; 10.1007/s43152-024-00056-3
7. Madeira A, Moura TF, Soveral G. Aquaglyceroporins: implications in adipose biology and obesity. Cell Mol Life Sci. 2015;72(4):759-71. Doi: 10.1007/s00018-014-1773-2
8. Janus ED, Laatikainen T, Dunbar JA, Kilkkinen A, Bunker SJ, Philpot B, et al. Overweight, obesity and metabolic syndrome in rural southeastern Australia. Med J Aust. 2007;187(3):147-52. Doi: 10.5694/j.1326-5377.2007.tb01171.x
9. Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, et al. Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem. 2005;280(16):15493-6. Doi: 10.1074/jbc.C500028200
10. Rodríguez A, Gena P, Méndez-Giménez L, Rosito A, Valentí V, Rotellar F, et al. Reduced hepatic aquaporin-9 and glycerol permeability are related to insulin resistance in non-alcoholic fatty liver disease. Int J Obes (Lond). 2014;38(9):1213-20. Doi: 10.1038/ijo.2013.234
11. Bi Y, Pang S, Liu Y, Cheng J, Ma Q, Song A, et al. Aquaporins in lipid metabolism: functions and regulation in health and disease. Lipids Health Dis. 2025;24(1):336. https://doi.org/10.1186/s12944-025-02727-y
12. Galli M, Hameed A, Żbikowski A, Zabielski P. Aquaporins in insulin resistance and diabetes: more than channels! Redox Biol. 2021;44:102027. Doi: 10.1016/j.redox.2021.102027
13. Song WY, Wang Y, Hou XM, Tian CC, Wu L, Ma XS, et al. Different expression and localization of aquaporin 7 and aquaporin 9 in granulosa cells, oocytes, and embryos of patients with polycystic ovary syndrome and the negatively correlated relationship with insulin regulation. Fertil Steril. 2021;115(2):463-73. Doi: 10.1016/j.fertnstert.2020.08.015
14. Plaza A, Merino B, Ruiz-Gayo M. Cholecystokinin promotes functional expression of the aquaglycerol channel aquaporin 7 in adipocytes. Br J Pharmacol. 2022;179(16):4092-106. Doi: 10.1111/bph.15848
15. Méndez-Giménez L, Becerril S, Moncada R, Valentí V, Fernández S, Ramírez B, et al. Gastric plication improves glycemia partly by restoring the altered expression of aquaglyceroporins in adipose tissue and the liver in obese rats. Obes Surg. 2017;27(7):1763-74. https://doi.org/10.1007/s11695-016-2532-2
16. Calamita G, Delporte C. Involvement of aquaglyceroporins in energy metabolism in health and disease. Biochimie. 2021;188:20-34. Doi: 10.1016/j.biochi.2021.03.001
17. Xiang S, Tang X. Interfering with AQP1 alleviates ferroptosis, improves mitochondrial function and energy metabolic disorder in hypoxia/reoxygenation-induced H9c2 cardiomyocytes via Wnt/β-catenin pathway. Microvasc Res. 2025;160:104821. Doi: 10.1016/j.mvr.2025.104821
18. Qi Y, Xia W, Tao C, Fang X, Yu Y, Hu J, et al. AQP7-mediated mitochondrial redox homeostasis in vitrified oocytes: a genetic mechanism of PI3K/AKT signaling regulation. Genes (Basel). 2025;16(7):730. Doi: 10.3390/genes16070730
19. Khattab BA, Hammad MO, Eldken ZH, Hellal D, Mohamed SZ, Sakr NH. Impact of intermittent fasting versus vitamin D on high fat fructose-induced pancreatic steatosis: possible role of aquaporins. Mol Med. 2025;31(1):207. Doi: 10.1186/s10020-025-01239-w
20. Liu J, Xia Z, Peng S, Xia J, Xu R, Wang X, et al. The important role of aquaglyceroporin 7 in health and disease. Biomolecules. 2024;14(10):1228. Doi: 10.3390/biom14101228
21. da Silva IV, Díaz-Sáez F, Zorzano A, Gumà A, Camps M, Soveral G. Aquaglyceroporins are differentially expressed in beige and white adipocytes. Int J Mol Sci. 2020;21(2):610. Doi: 10.3390/ijms21020610
22. Nørholm A, Kjær IG, Søndergaard E, Nellemann B, Nielsen S, Lebeck J. Glycerol handling in paired visceral and subcutaneous adipose tissues in women with normal weight and upper-body obesity. Int J Mol Sci. 2024;25(16):9008. Doi; 10.3390/ijms25169008
23. Wawrzkiewicz-Jałowiecka A, Lalik A, Soveral G. Recent update on the molecular mechanisms of gonadal steroids action in adipose tissue. Int J Mol Sci. 2021;22(10):5226. Doi: 10.3390/ijms22105226
24. da Silva IV, Gullette S, Florindo C, Huang NK, Neuberger T, Ross AC, et al. The effect of nutritional ketosis on aquaporin expression in apolipoprotein E-deficient mice: potential implications for energy homeostasis. Biomedicines. 2022;10(5):1159. Doi: 10.3390/biomedicines10051159
25. Khalil M, Gena P, Di Ciaula A, Portincasa P, Calamita G. Aquaporins in biliary function: pathophysiological implications and therapeutic targeting. Int J Mol Sci. 2024;25(22):12133. Doi: 10.3390/ijms252212133
26. Charlestin V, Fulkerson D, Arias Matus CE, Walker ZT, Carthy K, Littlepage LE. Aquaporins: new players in breast cancer progression and treatment response. Front Oncol. 2022;12:988119. https://doi.org/10.3389/fonc.2022.988119
27. Palabiyik O, Kilic-Toprak E, Sumnulu D, Tozkir J, Cort A. Effect of lemon verbena polyphenol on glycerol channel aquaporin 7 expression in 3T3-L1 adipocytes. Experimed. 2024;14(2):102-9. Doi: 10.26650/experimed.1479944
28. Elhessy HM, Berika M, Salem YG, El-Desoky MM, Eldesoqui M, Mostafa N, et al. Therapeutic effects of intermittent fasting on high-fat, high-fructose diet; involvement of jejunal aquaporin 1, 3, and 7. Heliyon. 2024;10(7):e28436. https://doi.org/10.1016/j.heliyon.2024.e28436
29. Shangzu Z, Dingxiong X, ChengJun M, Yan C, Yangyang L, Zhiwei L, et al. Aquaporins: important players in the cardiovascular pathophysiology. Pharmacol Res. 2022;183:106363. Doi: 10.1016/j.phrs.2022.106363
30. Iena FM, Kalucka J, Nielsen L, Søndergaard E, Nielsen S, Lebeck J. Localization of aquaglyceroporins in human and murine white adipose tissue. Histochem Cell Biol. 2022;157(6):623-39. Doi: 10.1007/s00418-022-02090-4
31. Frühbeck G, Méndez-Giménez L, Becerril S, Ramírez B, Hernández-Pardos AW, Cienfuegos JA, et al. Increased aquaporin-7 expression is associated with changes in rat brown adipose tissue whitening in obesity: impact of cold exposure and bariatric surgery. Int J Mol Sci. 2023;24(4):3412. Doi: 10.3390/ijms24043412
32. Trinchese G, Gena P, Cimmino F, Cavaliere G, Fogliano C, Garra S, et al. Hepatocyte aquaporins AQP8 and AQP9 are engaged in the hepatic lipid and glucose metabolism modulating the inflammatory and redox state in milk-supplemented rats. Nutrients. 2023;15(16):3651. doi.org/10.3390/nu15163651
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Copyright (c) 2026 Oscar Jhoan Castro Zevallos, Mariafernanda Perez Vega, Daniel Sebastian Peña Saavedra, Diana Moreno Chávez
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