Palabras clave
Ácidos grasos
Ácido oleico
Ácido palmítico
Resistencia a la insulina
Insulina
Lipolisis
Lipogénesis
Cómo citar
Resumen
Introducción: Los niveles elevados de ácidos grasos libres (AGL) en suero inducen resistencia a insulina (RI) o un mecanismo de protección del desarrollo de RI en humanos, esto depende del tipo de AGL. Este estudio explora los efectos de los ácidos grasos oleico (insaturados – OLA) y palmítico (saturados-PAM) sobre la insulina en adipocitos maduros. Métodos: Las células se incubaron 18 h con o sin OLA y PAM a 250 μM y 500 μM. Después del período de cultivo, se evaluó en adipocitos: viabilidad, tamaño, movilización de ácidos grasos, proteínas de señalización de insulina y absorción de glucosa. Resultados: Los adipocitos mostraron viabilidad óptima independientemente de los tipos de ácidos grasos utilizados en el tratamiento. Los adipocitos eran hipertróficos tras estimulo con OLA y PAM. La lipogénesis (síntesis de lípidos) y la lipólisis (degradación de lípidos) aumentaron significativamente con el tratamiento con OLA o PAM (500 μM) en comparación con el control. En los resultados de OLA no se evidenció una reducción significativa en las cascadas de señalización de insulina, a excepción de una respuesta proinflamatoria posterior. En cambio, los adipocitos hipertróficos tratados con PAM presentaron resistencia a la insulina y alteración de los marcadores proinflamatorios y de estrés. Conclusiones: Nuestros hallazgos sugieren que PAM induce resistencia a la insulina, estrés mitocondrial y del retículo en las células grasas en comparación con aquellos tratados con OLA, AGL que, en cambio, protegen a los adipocitos de todas esas alteraciones.
Referencias
Daryabor G, Dieter K, Kurosh K. An Update on immune dysregulation in obesity-related insulin resistance. Scand J Immunol. 2019; 89(4): e12747. doi: 10.1111/sji.12747
Li Y, Quantao M, Pengfei L, Jingkang W, Min Wang Y, Fan Tieshan W, et al. Proteomics Reveals Different Pathological Processes of Adipose Tissue, Liver, and Skeletal Muscle under Insulin Resistance. J Cellular Physiol. 2020; 235(10): 1-21. doi: https://doi.org/10.1002/jcp.29658
Blüher M. Metabolically healthy obesity. Endocrine Reviews. 2020; 41(3): 405-420. doi: https://doi.org/10.1210/endrev/bnaa004
Schulze MB. Metabolic health in normal-weight and obese individuals. Diabetologia. 2019; 62(4): 558-566. doi: 10.1007/s00125-018-4787-8
Hinnouho GM, Czernichow S, Dugravot A, David B, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and risk of mortality: Does the definition of metabolic health matter? Diabetes Care. 2013; 36(8): 2294-2300. doi: 10.2337/dc12-1654
Stefan N, Hans UH, Frank BH, Matthias BS. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013; 1(2): 152-162. doi: 10.1016/S2213-8587(13)70062-7
Meng H, Nirupa RM, Dayong W, Lijun L, Rodríguez-Morató J, Cohen R, et al. Comparison of diets enriched in stearic, oleic, and palmitic acids on inflammation, immune response, cardiometabolic risk factors, and fecal bile acid concentrations in mildly hypercholesterolemic postmenopausal women - randomized crossover trial. Am J Clin Nutr. 2019; 110(2): 305-315. doi: 10.1093/ajcn/nqz095
Ruan H, Harvey FL. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α. Cytokine Growth Factor Rev. 2003; 14(5): 447-55. doi: 10.1016/s1359-6101(03)00052-2
Jager J, Grémeaux T, Cormont M, Marchand- Brustel YL, Tanti JF. Interleukin-1β-Induced Insulin Resistance in Adipocytes through down-Regulation of Insulin Receptor Substrate-1 Expression. Endocrinology. 2007; 148(1): 241-251. doi: https://doi.org/10.1210/en.2006-0692
Thomson MJ, Williams MG, Frost SC. Development of Insulin Resistance in 3T3-L1 Adipocytes. J Biol Chem. 1997; 272(12): 7759-7764. doi: https://doi.org/10.1074/jbc.272.12.7759
Regazzetti C, Peraldi P, Grémeaux T, Najem- Lendom R, Ben-Sahra I, Cormont M, et al. Hypoxia decreases insulin signaling pathways in adipocytes. Diabetes. 2009; 58(1): 95-103. doi: 10.2337/db08-0457
Lo KA, Labadorf A, Kennedy NJ, Han MS, Yap YS, Matthews B, et al. Analysis of in vitro insulin-resistance models and their physiological relevance to InVivo diet-induced adipose insulin resistance. Cell Reports. 2013; 5(1): 259-270. doi: https://doi.org/10.1016/j.celrep.2013.08.039
Shapiro AL, Ringham BM, Glueck DH, Norris JM, Barbour LA, Friedman JE, et al. Infant adiposity is independently associated with a maternal high fat diet but not related to niacin intake: The healthy start study. matern child health J. 2017; 28(8): 1662- 1668. doi: 10.1007/s10995-016-2258-8
Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, et al. JNK and tumor necrosis factor-α mediate free fatty acid-induced insulin resistance in 3T3-L1 Adipocytes. J Biol Chem. 2005; 280(42): 35361-35371. doi: 10.1074/jbc.M504611200
Guo W, Wong S, Xie W, Lei T, Luo Z. et al. Palmitate Modulates Intracellular Signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab. 2007; 293(2): E576-86. doi: 10.1152/ajpendo.00523.2006
Oliveira V, Marinho R, Vitorino D, Santos GA, Moraes JC, Dragano N, et al. Diets containing α-linolenic (Ω3) or Oleic (Ω9) fatty acids rescues obese mice from insulin resistance. Endocrinology. 2015; 156(11): 4033-4046. doi: 10.1210/en.2014-1880
Moreno-Castellanos N, Rodríguez A, Rabanal- Ruiz Y, Fernández-Vega A, López-Miranda J, Vázquez-Martínez R, et al. The Cytoskeletal protein septin 11 Is Associated with human obesity and is involved in adipocyte lipid storage and metabolism. Diabetología. 2017; 60(2): 324-235. doi: 10.1007/s00125-016-4155-5
Azahari N, Muhammad M, Ali Khan K, Muhammad T, Solachuddin J, Arief I. Dose water extract of cinnamon (Cinnamomum Zeylanicum) exhibits anti-diabetic properties in cultured 3T3-L1 adipocytes: A concurrent assessment of adipogenesis, lipolysis and glucose uptakes. J Food Nutrition Res. 2014; 2(11): 764-769. doi: 10.12691/jfnr-2-11-1
Díaz-Ruiz A, Guzmán-Ruiz R, Moreno NR, García-Rios A, Delgado-Casado N, Membrives A, et al. 2015. Proteasome dysfunction associated to oxidative stress and proteotoxicity in adipocytes compromises insulin sensitivity in human obesity. Antioxid Redox Signal. 2015; 23(7): 597-612. doi: 10.1089/ars.2014.5939
Bolsoni-Lopes A, Festuccia WT, Chimin P, Farias T, Torres-Leal FL, Cruz MM, et al. Palmitoleic Acid (n-7) increases white adipocytes GLUT4 Content and glucose uptake in association with AMPK Activation. Lipids Health Dis. 2014; 13(99). doi: 10.1186/1476-511X-13-199
D’Esposito V, Passaretti F, Hammarstedt A, Liguoro D, Terracciano D, Molea G, et al. Adipocyte- Released Insulin-like Growth Factor-1 Is Regulated by Glucose and Fatty Acids and Controls Breast Cancer Cell Growth in Vitro. Diabetologia. 2012; 55(10): 2811-2822. doi: 10.1007/s00125-012-2629-7
Palomer X, Pizarro-Delgado J, Barroso E, Vázquez- Carrera M. Palmitic and oleic acid: the yin and yang of fatty acids in Type 2 Diabetes Mellitus. Trends Endocrinol Metab. 2018; 29(3): 178-190. doi: 10.1016/j.tem.2017.11.009
Coll T, Eyre E, Rodríguez-Calvo R, Palomer X, Sánchez RM, Merlos M, et al. Oleate Reverses Palmitate-Induced Insulin Resistance and Inflammation in Skeletal Muscle Cells. J Biol Chem. 2008; 283(17): 11107-11116. doi: 10.1074/jbc.M708700200
Gong P, Li L, Liu Y, Pu J, Zhang S, Yu J, et al. Oleate Blocks Palmitate-Induced Abnormal Lipid Distribution, Endoplasmic Reticulum Expansion and Stress, and Insulin Resistance in Skeletal Muscle. Endocrinology. 2011; 152(6): 2206-2218. doi: 10.1210/en.2010-1369
Meric Erikci E, Hotamisligil GS. Lipid Signaling and Lipotoxicity in Metaflammation: Indications for Metabolic Disease Pathogenesis and Treatment. J Lipid Res. 2016; 57(12): 2099-2114. doi: 10.1194/jlr.R066514
Gonzalez-Franquesa A, Patti ME. Insulin resistance and mitochondrial dysfunction. In Adv Exp Med Biol. 2017; 465-520. doi: 10.1007/978-3-319-55330-6_25
Tumova JM, Trnka J. Excess of Free Fatty Acids as a Cause of Metabolic Dysfunction in Skeletal Muscle. Physiol Res. 2016; 65(2): 193-207. doi: 10.33549/physiolres.932993
Bhagirath C, Summers SA. Ceramides - Lipotoxic Inducers of Metabolic Disorders. Trends Endocrinol Metab. 2015; 26(10): 538-550. doi: 10.1016/j.tem.2015.07.006
Moreno-Castellanos N, Guzmán-Ruiz R, Cano DA, Madrazo-Atutxa A, Peinado JR, Pereira-Cunillet JL, et al. The effects of bariatric surgery-induced weight loss on adipose tissue in morbidly obese women depends on the initial metabolic status. Obes Surg. 2016; 26(8): 1757-1767. doi: 10.1007/s11695-015-1995-x
Harrison SA, Clancy BM, Pessino A, Czech MP. Activation of Cell Surface Glucose Transporters Measured by Photoaffinity Labeling of Insulin- Sensitive 3T3-L1 Adipocytes. J Biol Chem. 1992; 267(6): 3783-3788. doi: https://doi.org/10.1016/S0021-9258(19)50594-4
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Derechos de autor 2021 Natalia Rocio Moreno–Castellanos, Alberto Angel–Martin, Gerardo Mantilla–Mora