Envolvimento da inflamação subclínica e do estresse oxidativo na resistência à insulina associada a obesidade.

Palavras-chave: Pos-graduação em Saúde

Resumo

A epidemia global da obesidade é um dos mais importantes problemas de saúde pública. Excessiva adiposidade é um crucial fator de risco no surgimento de várias doenças metabólicas, incluindo hipertensão, diabetes mellitus do tipo 2 e doença do fígado gorduroso não alcoólico.  Essas condições patológicas estão estritamente associadas com a resistência à insulina. Baseado nos esforços das últimas décadas, ocorreu marcante desenvolvimento na investigação sobre resistência à insulina induzida pela obesidade, especialmente em termos do mecanismo envolvido neste processo. Dentre esses, a inflamação subclínica ou crônica de baixo grau na obesidade tem sido o mais aceito. Este estado inflamatório é caracterizado por altos níveis circulantes de citocinas inflamatórias, incluindo TNF alfa e IL beta, e aumentado infiltração de macrófagos em tecidos periféricos. No entanto, recentemente, tem ocorrido grande interesse no papel que o estresse oxidativo desempenha na indução da resistência à insulina. Sob ativação, muitas células imunes geram radicais livres e, da mesma maneira, a síntese de espécies reativas de oxigênio promovem um status inflamatório. Estudos têm mostrado níveis elevados de espécies reativas e estresse oxidativo em indivíduos e animais obesos e/ou resistentes a insulina; isso parece estar associado a redução da função e da atividade e biogênese mitocondrial causada pelo aumento de lipídeos circulantes e maior deposição de gordura ectópica.  Essa revisão discorre sobre o mecanismo fisiopatológico de como a inflamação subclínica induz resistência à insulina na obesidade. Ainda, descreve o papel que o estresse oxidativo desempenha neste processo, bem como a produção de radicais livres na obesidade.

Referências

AGUIRRE, V. et al. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. v. 275, n. 12, p. 9047-9054, Mar. 2000

Alessi, D.R.; Cohen, P. Mechanism of activation and function of protein kinase B. Curr Opin Genet Dev. v. 8, n. 1, p. 55-62, Fev. 1998

AMIRKHIZI, F. et al.. Is obesity associated with increased plasma lipid peroxidation and oxidative stress in women. ARYA Atheroscler. J. v. 2, p. 189–192. 2007

ARSLAN, N.; ERDUR, B.; AYDIN, A. Hormones and cytokines in childhood obesity. Indian Pediatr. v. 47, n. 10, p. 829-939, Out. 2010

BACKER, S.A.; KELLERMANN, J.; LOTTSPEICH, F. A phosphoproteomic study of insulin signaling pathway using a novel high-throughput pipeline. EMBO. J. v. 11, n. 9, p. 3469-3479, 1992

BARREIROS, A.; DAVID, J.M. Estresse Oxidativo: Relação entre geração de espécies reativas e defesa do organismo. Revista Química Nova. v. 29, n. 1, p. 113-123. 2006

BOURNAT, J.C.; BROWN, C.W. Mitochondrial dysfunction in obesity. Curr Opin Endocrinol Diabetes Obes. v. 17, n. 5, p. 446-452, Out. 2010

BRESTOFF, J.R.; ARTIS, D. Immune regulation of metabolic homeostasis in health and disease. Cell. v. 161, n. 1, p. 146-160. Mar. 2015

CAESAR, R. et al. Crosstalk between gut microbiota and dietary lipids aggravates WAT Inflammation through TLR signaling. Cell Metab. v. 22, n. 4, p. 658–668, Out. 2015

CALDER, P.C. N-3 fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clin. Sci. (London). v. 107. n. 1, p. 1–11, Jul. 2004

Cantley, L.C. The phosphoinositide 3-kinase pathway. Science. v. 296, n. 5573, p. 1655-1657, Mai. 2002.

COLLINS, K.H. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res. v. 7, n. 4, p. 274-281, Mai. 2018

DENG, L. et al. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. v. 103, n. 2, p. 351-361, Out. 2000;

DI MEO, S. ; IOSSA, S. ; VENDITTI, P. Skeletal muscle insulin resistance: role of mitochondria and other ROS sources. J Endocrinol. v. 233, n. 1, p. R15-R42, Abr. 2017

DROR, E. et al. Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nature Immunology. v. 18, n. 3, p. 283–292, Mar. 2017

DUVNJAK, M. et al. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J. Gastroenterol. v. 13, n. 34, p. 4539–4550, Set. 2007

EGNATCHIK, R.A. et al. Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes. Metabolism. v. 63, n. 2, p. 283-95, Fev. 2014

FERNÁNDEZ-SÁNCHEZ, A. et al. Inflammation, oxidative stress, and obesity. Int. J. Mol. Sci. v. 12, n. 5, p. 3117–3132, 2011

FROSSI, B. et al. Oxidative stress stimulates IL-4 and IL-6 production in mast cells by an APE/Ref-1-dependent pathway. Eur J Immunol. v. 33, n. 8, p. 2168-2177, Ago. 2003

FURUKAWA, S. et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. v. 114, n. 12, p. 1752-1761, Dez. 2004;

GAELIC, S.; OAKHILL, J.S.; STEINBERG, G.R. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. v. 316, n. 2, p. 129-139, Mar. 2010;

GOOSSENS, G.H. The role of adipose tissue dysfunction in the pathogenesis of obesity- related insulin resistance. Physiol. Behav. v. 94, n. 2, p. 206–218. Mai. 2008

HAN, C.Y. et al. NADPH oxidase-derived reactive oxygen species increases expression of monocyte chemotactic factor genes in cultured adipocytes. J Biol Chem. v. 287, n. 13, p. 10379-10393, Mar. 2012

HENRIKSEN, E.; DIAMOND-STANIC, M.; MARCHIONNE, E. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. v. 51, p. 993e9, 2011

HIROSUMI, J. et al. A central role for JNK in obesity and insulin resistance. Nature. v. 420. n. 6913, p. 333-336, Nov. 2002

HOTAMISLIGIL, G.S.; SHARGILL, N.S.; SPIEGELMAN, B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. v. 259, n. 5091, p. 87-91, Jan. 1993

HOTAMISLIGIL, G.S. Inflammation and metabolic disorders. Nature. v. 444. n. 7121, p. 860-867, Dez. 2006

HOUSTIS, N.E.; ROSEN, E.D.; LANDER, E.S. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. v. 440. n. 7086, p. 944-948, Abr. 2006

HURRLE, S.; HSU, W.H. The etiology of oxidative stress in insulin resistance. Biomed J. v. 40, n. 5, p. 257-262, Out. 2017

KHAN, N.; NAZ, L.; YASMEEN, G. Obesity: An independent risk factor systemic oxidative stress. Pak. J. Pharm. Sci. v. 19, n. 1, p. 62–69, Jan. 2006

KIM, J.A.; WEI, Y.; SOWERS, J.R. Role of mitochondrial dysfunction in insulin resistance. Circ Res. v. 102, n. 4, p. 401-414, Fev. 2008

KORSHUNOV, S.S.; SKULACHEV, V.P.; STARKOV, A.A. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett. v. 416, n. 1, p.15-18, Out. 1997

KRISHNAN, S.; COOPER, J.A. Effect of dietary fatty acid composition on substrate utilization and body weight maintenance in humans. Eur J Nutr. v. 53, n. 3, p. 691-710, 2014

LANCASTER, G.I. et al. Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism. Cell Metab. v. 27, n. 5, p. 1096-1110.e5, Mai. 2018

LARANCE, M. et al. Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking. J Biol Chem. v. 280, n. 45, p. 37803-37813, Nov. 2005

LARK, D.S. et al. Enhanced mitochondrial superoxide scavenging does not improve muscle insulin action in the high fat-fed mouse. PLoS One. v. 10, n. 5, p. e0126732, 2015

LEE, H.Y. et al. Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. Cell Metab. v. 12, n. 6, p. 668-674, Dez. 2010

MANNING, P.J. et al. Postprandial cytokine concentrations and meal composition in obese and lean women. Obesity. v. 16, n. 9, p. 2046-2052, Set. 2008

MARSEGLIA, L. et al. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. v. 16, n. 1, p. 378-400, Dez. 2014

MATSUO, M.; KANEKO, T. The chemistry of reactive oxygen species and related free radicals. In: Radák, Z. Free Radicals in Exercise and Aging Champaign. Human Kinetics. New Zealand: 33 F. 2001.

NAKAMURA, K.; FUSTER, J.J.; WALSH, K. Adipokines: A link between obesity and cardiovascular disease. J Cardiol. v. 63, n. 4, p. 250-259, Abr. 2014

OZATA, M. et al. Increased oxidative stress and hypozincemia in male obesity. Clin. Biochem. v. 35, n. 8, p. 627–631. Nov. 2002

PATEL, P.S.; BURAS, E.D.; BALASUBRAMANYAM, A. The role of the immune system in obesity and insulin resistance. J Obes. 616193, 2013

PIERI, B.L.S. Participação das espécies reativas na resistência muscular à insulina em camundongos com obesidade induzida por dieta hiperlipídica. 57 f. Tese (programa de pós-graduação em ciências da saúde). Universidade do Extremo Sul Catarinense, Criciúma, 2017

SALTIEL, A.; KAHN, C.R. Insulin signaling and the regulation of glucose and lipid metabolism. Nature. v. 414, n. 6865, p. 799-806, Dez. 2001;

SERRA, D. et al. Mitochondrial fatty acid oxidation in obesity. Antioxid Redox Signal. v. 19, n. 3, p. 269–284, Jul. 2013

SHOELSON, S.E.; LEE, J.; YUAN, M. Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord. v. 27, n. 3, p. S49-52, Dez. 2003

SHOELSON, S.E.; HERRERO, L.; NAAZ, A. Obesity, inflammation, and insulin resistance. GASTROENTEROLOGY. v. 132, n. 6, p. 2169–2180, Mai. 2007

SONNENBURG, J.L.; BÄCKHED, F. Diet-microbiota interactions as moderators of human metabolism. Nature. v. 535, n. 7610, p. 56-64, Jul. 2016

ARCHULETA T.L. et al. Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: Role of p38 MAPK. Free Radic Biol Med. v. 47, n. 10, p. 1486-1493, Nov. 2009

TATEYA, S.; KIM, F.; TAMORI, Y. Recent advances in obesity-induced inflammation and insulin resistance. Front Endocrinol (Lousanne). v. 4, n. 93, p. 1-14, Ago. 2003

TERESHIN, E.V. A role of fatty acids in the development of oxidative stress in aging. A hypothesis. Adv. Gerontol. v. 20, n. 1, p. 59–65, 2007

TSAI K.H. et al. NADPH oxidase-derived superoxide anion-induced apoptosis is mediated via the JNK-dependent activation of NF-κB in cardiomyocytes exposed to high glucose. J Cell Physiol. V. 227, n. 4, p. 1347-57, Abr. 2012

TUNCMAN, G. et al. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci USA. v. 103, n. 28, p.10741-10746, Jul. 2006

URAKAWA, H. et al. Oxidative stress is associated with adiposity and insulin resistance in men. J Clin Endocrinol Metab. v. 88, n. 10, p. 4673-4676, Out. 2003

VESELY P,W. et al. Translational regulation mechanisms of AP-1 proteins. Mutat. Res. v. 682, n. 1, p. 7-12, Jul 2009

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Inves. v. 112, n. 12, p. 1796-1808, Dez. 2003

WENSVEEN, F.M. et al. Interactions between adipose tissue and the immune system in health and malnutrition. Semin Immunol. v. 27, n. 5, p. 322-333. Set. 2015

WILCOX, G. Insulin and insulin resistance. Clin Biochem Rev. v. 26, n. 2, p. 19-39, Mai. 2005

WILLIAMSON, RT. On the Treatment of Glycosuria and Diabetes Mellitus with Sodium Salicylate. Br Med J. v. 1, n. 2100, p. 760-762, Mar. 1901

XU, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. v. 112, n. 12, p. 1821-1830, Dez. 2003

YAMASAKI, M. et al. Vaccinium ashei leaves extract alleviates insulin resistance via AMPK independent pathway in C2C12 myotube model. Biochem Biophys Rep. v. 14, p. 182–187, Mai. 2018

YUAN, M. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. v. 293, n.5535, p. 1673-7, Ago. 2001

ZHANG, X. et al. Selective inactivation of c-Jun NH2-Terminal kinase in adipose tissue protects against diet induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice. Diabetes. v. 60, n. 2, p. 486-495, Fev. 2011.

Publicado
2019-04-04
Como Citar
Souza, C. T. (2019). Envolvimento da inflamação subclínica e do estresse oxidativo na resistência à insulina associada a obesidade. HU Revista, 44(2), 211 - 220. https://doi.org/10.34019/1982-8047.2018.v44.16950
Seção
Artigos de Revisão da Literatura