ADVERTISEMENT

ADVERTISEMENT

LIPOTOXICIDAD EN MÚSCULO ESQUELÉTICO Y SU RELACIÓN CON LA RESISTENCIA INSULÍNICA. ESTUDIOS EN UN MODELO EXPERIMENTAL DE SÍNDROME METABÓLICO

María Eugenia Oliva, María del Rosario Ferreira, Victoria Aiassa, María Eugenia D’Alessandro

Resumen


Introducción: el acúmulo de lípidos en el músculo esquelético se encuentra estrechamente vinculado con el desarrollo de la resistencia insulínica. Esta última cumple un rol patogénico central en el desarrollo de numerosos desórdenes metabólicos incluidos en el síndrome metabólico.
Objetivos: analizar algunas vías metabólicas implicadas en el acúmulo de lípidos en el músculo esquelético y su asociación con la resistencia insulínica en un modelo experimental que mimetiza el fenotipo del síndrome metabólico humano.
Materiales y métodos: ratas macho Wistar recibieron una dieta control (DC) o una dieta rica en sacarosa (DRS) durante seis meses. Al final del período experimental se analizó en músculo esquelético gastrocnemio: contenido de triglicéridos (TG), acil-CoA de cadena larga y diacilglicerol, actividad enzimática carnitina palmitoil transferasa muscular (M-CPT1, M-CPT2 y M-CPT total) y masa proteica del PPARα, AMPK y AMPKp. Se determinaron los niveles séricos de TG, AGNE, glucosa, insulina, TNFα y adiponectina. La sensibilidad insulínica se midió por la técnica clamp euglucémica-hiperinsulinémica.


Palabras clave


síndrome metabólico; dieta rica en sacarosa; músculo esquelético; resistencia insulínica; lipotoxicidad

Texto completo:

PDF

Referencias


Bruce K, Hanson M. The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr 2010; 5:648-52.

Carnagarin R, Dharmarajan AM, Dass CR. Molecular aspects of glucose homeostasis in skeletal muscle. A focus on the molecular mechanisms of insulin resistance. Mol Cell Endocrinol 2015; 417:52-62.

Turcotte LP, Fisher JS. Skeletal muscle insulin resistance: roles of fatty acid metabolism and exercise. Phys Ther 2008; 88(11): 1-18.

McGarry JD. Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51: 7-18.

Amati F, Dubé JJ, Alvarez-Carnero E, et al. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes 2011; 60: 2588-97.

Chavez JA, Knotts TA, Wang LP, et al. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 2003; 278(12): 10297-303.

Itani SI, Ruderman NB, Schmieder F, et al. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. Diabetes 2002; 51: 2005-11.

Turner N, Kowalski GM, Leslie SJ, et al. Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. Diabetologia 2013; 56(7): 1638-48.

Holloway GP, Luiken JJ, Glatz JFC, et al. Contribution of FAT/CD36 to the regulation of skeletal muscle fatty acid oxidation: an overview. Acta Physiol 2008; 194(4): 293-309.

Kiens B. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 2006;86(1): 205-43.

Burri L, Thoresen H, Berge RK. The role of PPARα activation in liver and muscle. PPAR Res 2010; pii: 542359. Doi: 10.1155/2010/542359.

Lyons C, Roche H. Nutritional modulation of AMPK. Impact upon metabolic-inflammation. Int J Mol Sci 2018; 19: 3092-109.

Ruderman N, Carling D, Prentki M, et al. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest 2013; 123 (7): 2764-72.

Chicco A, Soria A, Gutman R, et al. Multiphasic metabolic changes in the heart of rats fed a sucrose-rich diet. Horm Metab Res 1994; 26: 397-403.

Chicco A, D’Alessandro ME, Karabatas R, et al. Muscle lipid metabolism and insulin secretion are altered in insulin-resistant rats fed a high sucrose diet. J Nutr 2003; 133(1): 127-33.

D’Alessandro ME, Chicco A, Lombardo YB. Fish oil reverses the altered glucose transporter, phosphorylation, insulin receptor substrate-1 protein level and lipid contents in the skeletal muscle of sucrose-rich diet fed rats. PLEFA 2012; 88(2): 171-77.

Reeves Nielsen FH, Fahey GC. AIN-93 Purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing Committee on the Reformulation of the AIN-76ª Rodent Diet. J Nutr 1993; 123(11): 1939-51.

D’Alessandro ME, Chicco A, Karabatas L, et al. Role of skeletal muscle on impaired insulin sensitivity in rats fed a sucrose-rich diet: effect of moderate levels of dietary fish oil. J Nutr Biochem 2000; 11(5):273-80.

D’Alessandro ME, Chicco AG, Lombardo YB. A long-term sucrose-rich diet increases diacylglycerol content and membrane nPKCθ expression and alters glucose metabolism in skeletal muscle of rats. Nutrition Research 2006; 26(6): 289-296.

Ling B, Aziz C, Alcorn J. Systematic evaluation of key L-carnitine homeostasis mechanisms during postnatal development in rat. Nutr Metab (Lond.) 2012; 9:66.

Creus A, Ferreira M, Oliva M, et al. Mechanisms involved in the improvement of lipotoxicity and impaired lipid metabolism by dietary α-linolenic acid rich Salvia hispanica L (Salba) seed in the heart of dyslipemic insulin-resistant rats. J Clin Med 2016; 28: 5(2). Doi: 10.3390/jcm5020018.

Oliva ME, Creus A, Ferreira MR, et al. Dietary soya protein improves intra-myocardial lipid deposition and altered glucose metabolism in a hypertensive, dyslipidaemic, insulin-resistant rat model. Br J Nutr 2018; 119(2): 131-42.

Snedecor GWP, Cochran WG. Statistical methods. Ames (Iowa): Iowa University Press 1967; 339-350.

Wieser V, Moschen A, Tilg H. Inflammation, cytokines and insulin resistance: a clinical perspective. Arch Immunol Ther Exp 2013; 61: 119-25.

Ziemke F, Mantzoros C. Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr 2010; 91(suppl):258S-61S.

Lombardo YB, Chicco A. Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review. J Nutr Biochem 2006; 17:1-13.

D’Alessandro ME, Selenscig D, Illesca P, et al. Time course of adipose tissue dysfunction associated with antioxidant defense, inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats. Food Funct 2015; 6(4):1299-1309.

Bi Y, Cai M, Liang H, et al. Increased carnitine palmitoyl transferase 1 expression and decreased sterol regulatory element-binding protein 1c expression are associated with reduced intramuscular triglyceride accumulation after insulin therapy in high-fat-diet and streptozotocin-induced diabetic rats. Metabolism 2009; 58(6):779-86.

Perdomo G, Commerford SR, Richard AMT, et al. Increased beta-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid-induced insulin resistance despite intramyocellular lipid accumulation. J Biol Chem 2004; 279(26):27177-86.

Kim J, Hickner R, Cortright R, et al. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 2000; 279: E1039–E44.




Copyright (c) 2019 Sociedad Argentina de Diabetes Asociación Civil

ADVERTISEMENT

ADVERTISEMENT