Rev Med UAS
Vol. 12: No. 4. Octubre-Diciembre 2022
ISSN 2007-8013

Estructura, señalización y regulación de la adiponectina en relación con la sensibilidad a la insulina y diabetes gestacional: Hallazgos clínicos y genéticos

Structure, signaling and regulation of adiponectin in relation to insulin sensitivity and gestational diabetes: clinical and genetic findings

Alba Esthela López-Quintero1, Itzel Irazú Cotero-de la Torre5, Karla Mayela Bravo-Villagra5, Adrián Herrera-Salazar2, Verónica Judith Picos-Cárdenas3, Fred Morgan-Ortíz2, Irak Mijail Trapero-Corona2, José Francisco Muñoz-Valle4*, Andres López-Quintero5

  1. Servicio de Ginecología y Obstetricia. Hospital Civil de Culiacán
  2. Servicio de Ginecología y Obstetricia. Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa.
  3. Laboratorio de Genética, Facultad de Medicina, Universidad Autónoma de Sinaloa.
  4. Instituto de Investigación en Ciencias Biomédicas, Universidad de Guadalajara.
  5. Instituto de Nutrigenética y Nutrigenómica Traslacional, Universidad de Guadalajara.

* Correspondencia: (Autoría compartida)
José Francisco Muñoz Valle. Instituto de Investigación en Ciencias Biomédicas, Universidad de Guadalajara. Correo electrónico: biologiamolecular@hotmail.com
Andrés López Quintero. Instituto de Nutrigenética y Nutrigenómica Traslacional, Universidad de Guadalajara. Sierra Mojada 950, Puerta 7, Edificio Q, Primer Piso. Colonia Independencia, C.P. 44340. Guadalajara, Jalisco, México. Correo electrónico: andres.lopezq@academicos.udg.mx +52(33)1058 5200 (ext. 33644)

DOI http://dx.doi.org/10.28960/revmeduas.2007-8013.v12.n4.010

Texto Completo PDF

Recibido 30 de abril de 2022, aceptado 21 de octubre de 2022

RESUMEN
El tejido adiposo sintetiza y secreta una serie de moléculas que intervienen en diversos procesos como la homeostasis energética, inmunidad e inflamación. La adiponectina está involucrada en el control de la homeostasis en tejidos sensibles a la insulina; se encuentra principalmente en circulación cómo oligómeros de distintos pesos moleculares que activan diversas vías de señalización. La implicación de adiponectina y sus isoformas en la regulación de la homeostasis energética y su posible uso como biomarcador pronóstico en la sensibilidad a la insulina generan la necesidad de conocer el impacto de intervenciones que modifiquen sus niveles circulantes o de expresión. Este conocimiento es particularmente importante en la búsqueda de estrategias para mejorar el estado metabólico de sujetos en condiciones metabólicas alteradas como la diabetes gestacional. Por lo que el objetivo de esta revisión fue integrar el conocimiento para mejorar la comprensión sobre la regulación de adiponectina y su aplicación clínica.
Palabras clave: Adiponectina, ADIPOQ, resistencia a la insulina, diabetes gestacional.

ABSTRACT
Adipose tissue synthesizes and secretes a series of molecules implicated in various processes such as energy homeostasis, immunity, and inflammation. Adiponectin is involved in the control of homeostasis in insulin-sensitive tissues; it is mainly found in circulation as oligomers of different molecular weights that activate diverse signaling pathways. The role of adiponectin and its isoforms in the regulation of energy homeostasis and its possible use as a prognostic biomarker in insulin sensitivity, generate the need to know the impact of interventions that modify its circulating or expression levels. This knowledge is particularly important in the search for strategies to improve the metabolic status of subjects with altered metabolic conditions such as gestational diabetes. Therefore, the objective of this review was to integrate knowledge to improve understanding of adiponectin regulation and its clinical application.
Keywords: Adiponectin, ADIPOQ, insulin resistance, gestational diabetes mellitus.

Referencias

  1. Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013 Feb;417:80–4.
  2. Tsiotra PC, Halvatsiotis P, Patsouras K, Maratou E, Salamalekis G, Raptis SA, et al. Circulating adipokines and mRNA expression in adipose tissue and the placenta in women with gestational diabetes mellitus. Peptides. 2018 Mar;101:157–66.
  3. Xita N, Tsatsoulis A. Adiponectin in Diabetes Mellitus. Curr Med Chem. 2012 Oct 1;19(32):5451–8.
  4. Katsiki N, Mantzoros C, Mikhailidis DP. Adiponectin, lipids and atherosclerosis. Curr Opin Lipidol. 2017 Aug;28(4):347–54.
  5. Diep Nguyen T. Adiponectin: Role in physiology and pathophysiology. Int J Prev Med. 2020;11(1):136.
  6. Gu W, Li Y. The Therapeutic Potential of the Adiponectin Pathway. 2012;8.
  7. Combs TP, Marliss EB. Adiponectin signaling in the liver. Rev Endocr Metab Disord. 2014 Jun;15(2):137–47.
  8. Ruan H, Dong LQ. Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol. 2016 Apr;8(2):101–9.
  9. Liu M, Liu F. Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab. 2014 Jan;28(1):25–31.
  10. Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol. 2014;13(1):103.
  11. Caselli C. Role of adiponectin system in insulin resistance. Mol Genet Metab. 2014 Nov;113(3):155–60.
  12. Shehzad A, Iqbal W, Shehzad O, Lee YS. Adiponectin: Regulation of its production and its role in human diseases. Hormones. 2012 Jan;11(1):8–20.
  13. Cheng KKY, Lam KSL, Wang B, Xu A. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin. Best Pract Res Clin Endocrinol Metab. 2014 Jan;28(1):3–13.
  14. Fu Y. Adiponectin Signaling and Metabolic Syndrome. In: Progress in Molecular Biology and Translational Science [Internet]. Elsevier; 2014 [cited 2022 Jan 24]. p. 293–319. Available from: https://n9.cl/0tofm
  15. Esmaili S, Hemmati M, Karamian M. Physiological role of adiponectin in different tissues: a review. Arch Physiol Biochem. 2020 Jan 1;126(1):67–73.
  16. Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T. Adiponectin receptors: A review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 2014 Jan;28(1):15–23.
  17. Roy B, Palaniyandi SS. Tissue-specific role and associated downstream signaling pathways of adiponectin. Cell Biosci. 2021 Dec;11(1):77.
  18. J. Hickman I, P. Whitehead J. Structure, Signalling and Physiologic Role of Adiponectin-Dietary and Exercise- Related Variations. Curr Med Chem. 2012 Oct 1;19(32):5427–43.
  19. Aye ILMH, Powell TL, Jansson T. Review: Adiponectin – The missing link between maternal adiposity, placental transport and fetal growth? Placenta. 2013 Mar;34:S40–5.
  20. Choi HM, Doss HM, Kim KS. Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases. Int J Mol Sci. 2020 Feb 12;21(4):1219.
  21. Van Andel M, Heijboer AC, Drent ML. Adiponectin and Its Isoforms in Pathophysiology. In: Advances in Clinical Chemistry [Internet]. Elsevier; 2018 [cited 2022 Jan 24]. p. 115–47. Available from: https://n9.cl/6caap
  22. Tabb KL, Gao C, Hicks PJ, Hawkins GA, Rotter JI, Chen Y-DI, et al. Adiponectin Isoform Patterns in Ethnic-Specific ADIPOQ Mutation Carriers: The IRAS Family Study: Adiponectin Isoforms in ADIPOQ Mutation Carriers. Obesity. 2017 Aug;25(8):1384–90.
  23. Fang H, Judd RL. Adiponectin Regulation and Function. In: Terjung R, editor. Comprehensive Physiology [Internet]. 1st ed. Wiley; 2018 [cited 2022 Jan 24]. p. 1031–63. Available from: https://n9.cl/a4ckf
  24. Balsan GA, Vieira JL da C, Oliveira AM de, Portal VL. Relationship between adiponectin, obesity and insulin resistance. Rev Assoc Médica Bras. 2015 Feb;61(1):72–80.
  25. Tishinsky JM, Robinson LE, Dyck DJ. Insulin-sensitizing properties of adiponectin. Biochimie. 2012 Oct;94(10):2131–6.
  26. Jaganathan R, Ravindran R, Dhanasekaran S. Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease. Can J Diabetes. 2018 Aug;42(4):446-456.
  27. Engin A. Adiponectin-Resistance in Obesity. In: Engin AB, Engin A, editors. Obesity and Lipotoxicity [Internet]. Cham: Springer International Publishing; 2017 [cited 2022 Jan 24]. p. 415–41. (Advances in Experimental Medicine and Biology; vol. 960). Available from: https://n9.cl/4flst
  28. Zhao L, Fu Z, Liu Z. Adiponectin and insulin cross talk: The microvascular connection. Trends Cardiovasc Med. 2014 Nov;24(8):319–24.
  29. Park SE, Park C-Y, Sweeney G. Biomarkers of insulin sensitivity and insulin resistance: Past, present and future. Crit Rev Clin Lab Sci. 2015 Jul 4;52(4):180–90.
  30. Stears A, O’Rahilly S, Semple RK, Savage DB. Metabolic insights from extreme human insulin resistance phenotypes. Best Pract Res Clin Endocrinol Metab. 2012 Apr;26(2):145–57.
  31. Mather KJ, Goldberg RB. Clinical use of adiponectin as a marker of metabolic dysregulation. Best Pract Res Clin Endocrinol Metab. 2014 Jan;28(1):107–17.
  32. De Gennaro G, Palla G, Battini L, Simoncini T, Del Prato S, Bertolotto A, et al. The role of adipokines in the pathogenesis of gestational diabetes mellitus. Gynecol Endocrinol. 2019 Sep 2;35(9):737–51.
  33. De Luis DA, Izaola O, Primo D, Aller R. Single nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 interact with different type of dietary fatty acids in two hypocaloric diets. 2019; 23: 2960-2970
  34. AlSaleh A, Sanders TAB, O’Dell SD. Effect of interaction between PPARG, PPARA and ADIPOQ gene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study. Proc Nutr Soc. 2012 Feb;71(1):141–53.
  35. Aller R, Izaola O, Primo D, de Luis DA. The effect of single-nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 on metabolic parameters after 9 mo of a high-protein/low-carbohydrate versus a standard hypocaloric diet. Nutrition. 2019 Sep;65:44–9.
  36. Lowry DE, Fenwick PH, Roke K, Jeejeebhoy K, Dhaliwal R, Brauer P, et al. Variants in APOA5 and ADIPOQ Moderate Improvements in Metabolic Syndrome during a One-Year Lifestyle Intervention. Lifestyle Genomics. 2018;11(2):80–9.
  37. De Luis DA, Izaola O, Primo D, Gómez-Hoyos E, Ortola A, López-Gómez JJ, et al. Role of rs1501299 variant in the adiponectin gene on total adiponectin levels, insulin resistance and weight loss after a Mediterranean hypocaloric diet. Diabetes Res Clin Pract. 2019 Feb;148:262–7.
  38. De Luis DA, Primo D, Izaola O. Adiponectin gene variant rs266729 interacts with different macronutrient distributions of two different hypocaloric diets during nine months. Nutr Hosp [Internet]. 2021 [cited 2022 Jan 24]; Available from: https://n9.cl/zb0nk
  39. Siitonen N, Pulkkinen L, Lindström J, Kolehmainen M, Eriksson JG, Venojärvi M, et al. Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study. BMC Med Genet. 2011 Dec;12(1):5.
  40. De Luis DA, Primo D, Izaola O, Aller R. Adiponectin Gene Variant rs266729 Interacts with Different Macronutrient Distribution of Two Different Hypocaloric Diets. Lifestyle Genomics. 2019 Nov;11(1):8–1.
  41. Sun Y, Li D, Li Q, Huang L, He Z, Zhang F, et al. Relationship between ADIPOQ gene polymorphism and lipid levels and diabetes. Biological Regulators. 2015 Feb;29(1):183–177.
  42. Du W, Li Q, Lu Y, Yu X, Ye X, Gao Y, et al. Genetic variants in ADIPOQ gene and the risk of type 2 diabetes: a case–control study of Chinese Han population. Endocrine. 2011 Dec;40(3):413–22.
  43. Kitamoto A, Kitamoto T, So R, Matsuo T, Nakata Y, Hyogo H, et al. ADIPOQ polymorphisms are associated with insulin resistance in Japanese women. Endocr J. 2015;62(6):513–21.
  44. Nomani H, Hesami O, Vaisi‐Raygani A, Tanhapour M, Bahrehmand F, Rahimi Z, et al. Association between the −11377 C/G and −11391 G/A polymorphisms of adiponectin gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes mellitus in population from the west of Iran, correlation with lipid profile. J Cell Biochem. 2019 Mar;120(3):3574–82.
  45. Belalcazar LM, Papandonatos GD, McCaffery JM, Peter I, Pajewski NM, Erar B, et al. A common variant in the CLDN7/ELP5 locus predicts adiponectin change with lifestyle intervention and improved fitness in obese individuals with diabetes. Physiol Genomics. 2015 Jun;47(6):215–24.
  46. Lee K-Y, Kang H-S, Shin Y-A. Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women. Gene. 2013 Mar;516(2):271–6.
  47. Hellwege JN, Palmer ND, Brown MW, Ziegler JT, An SS, Guo X, et al. Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels. Hum Genet. 2015 Feb;134(2):203–13.
  48. Baril-Gravel L, Labonté M-E, Couture P, Vohl M-C, Charest A, Guay V, et al. Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: A randomized crossover controlled intervention trial. Nutr Metab Cardiovasc Dis. 2015 Jan;25(1):52–9.
  49. Perfilyev A, Dahlman I, Gillberg L, Rosqvist F, Iggman D, Volkov P, et al. Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial. Am J Clin Nutr. 2017 Apr;105(4):991–1000.
  50. Moran CN, Barwell ND, Malkova D, Cleland SJ, McPhee I, Packard CJ, et al. Effects of diabetes family history and exercise training on the expression of adiponectin and leptin and their receptors. Metabolism. 2011 Feb;60(2):206–14.
  51. Moghadasi M, Mohebbi H, Rahmani-Nia F, Hassan-Nia S, Noroozi H, Pirooznia N. High-intensity endurance training improves adiponectin mRNA and plasma concentrations. Eur J Appl Physiol. 2012 Apr;112(4):1207–14.
  52. Aslfalah H, Jamilian M, Khosrowbeygi A. Elevation of the adiponectin/leptin ratio in women with gestational diabetes mellitus after supplementation with alpha-lipoic acid. Gynecol Endocrinol. 2019 Mar 4;35(3):271–5.
  53. Corrado F, D’Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes: Supplementation of myoinositol in gestational diabetes. Diabet Med. 2011 Aug;28(8):972–5.
  54. Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: A prospective, randomized, placebo-controlled study. Early Hum Dev. 2012 Jun;88(6):339–44.
  55. Aviram A, Shtaif B, Gat-Yablonski G, Yogev Y. The association between adipocytokines and glycemic control in women with gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2020 Jan 17;33(2):177–83.
  56. White SL, Lawlor DA, Briley AL, Godfrey KM, Nelson SM, Oteng-Ntim E, et al. Early Antenatal Prediction of Gestational Diabetes in Obese Women: Development of Prediction Tools for Targeted Intervention. PLoS ONE.M2016 Dec 8;11(12):e0167846.
  57. Migda M, Migda MS, Migda B, Krzyżanowska P, Wender-Ożegowska E. Components of metabolic syndrome in the first trimester of pregnancy as predictors of adverse perinatal outcome. Ginekologia Polska 2016;87(9): 644–650.
  58. Mousa A, Abell SK, Shorakae S, Harrison CL, Naderpoor N, Hiam D, et al. Relationship between vitamin D and gestational diabetes in overweight or obese pregnant women may be mediated by adiponectin. Mol Nutr Food Res. 2017 Nov;61(11):1700488.
  59. Li L-J, Rifas-Shiman SL, Aris IM, Young JG, Mantzoros C, Hivert M-F, et al. Associations of maternal and cord blood adipokines with offspring adiposity in Project Viva: is there an interaction with child age? Int J Obes. 2018 Apr;42(4):608–17.
  60. Migda M, Migda MS, Migda B, Wender-Ozegowska E. Maternal First trimester parameters in the prediction of excessive fetal growth in pregnant women with metabolic syndrome. Physiology Pharma. 2017;68(6):839-833.
  61. Noreña I, Pardo MP, Mockus I. Niveles séricos de adipocitocinas y resistencia a la insulina en el primer trimestre de gestación en adolescentes y su relación con el peso del recién nacido. Biomédica. 2018 Sep 1;38(3):427–36.
  62. Maitland RA, Seed PT, Briley AL, Homsy M, Thomas S, Pasupathy D, et al. Prediction of gestational diabetes in obese pregnant women from the UK Pregnancies Better Eating and Activity (UPBEAT) pilot trial. Diabet Med. 2014 Aug;31(8):963–70.
  63. Kim C, Christophi CA, Goldberg RB, Perreault L, Dabelea D, Marcovina SM, et al. Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes. Diabet Med. 2016 Jan;33(1):32–8.
  64. Durnwald CP, Downes K, Leite R, Elovitz M, Parry S. Predicting persistent impaired glucose tolerance in patients with gestational diabetes: The role of high sensitivity CRP and adiponectin. Diabetes Metab Res Rev. 2018 Feb;34(2):e2958.
  65. Honnorat D, Disse E, Millot L, Mathiotte E, Claret M, Charrie A, et al. Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes? Diabetes Metab. 2015 Nov;41(5):393–400.
  66. Mehmood S, Ye C, Connelly PW, Hanley AJ, Zinman B, Retnakaran R. Rising plasminogen activator inhibitor-1 and hypoadiponectinemia characterize the cardiometabolic biomarker profile of women with recent gestational diabetes. Cardiovasc Diabetol. 2018 Dec;17(1):133.
  67. Gunderson EP, Kim C, Quesenberry CP, Marcovina S, Walton D, Azevedo RA, et al. Lactation intensity and fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin in postpartum women with recent gestational diabetes mellitus: The SWIFT cohort. Metabolism. 2014 Jul;63(7):941–50.
  68. Sun X, Sun H, Zhang J, Ji X. Artemisia Extract Improves Insulin Sensitivity in Women With Gestational Diabetes Mellitus by Up-Regulating Adiponectin: Artemisia Improves Insulin Sensitivity in GDM. J Clin Pharmacol. 2016 Dec;56(12):1550–4.