Associação do fator de necrose tumoral-alfa (TNF-α) com a obesidade
Resumo
Este trabalho teve como objetivo avaliar a associação entre o Fator de Necrose Tumoral–alfa (TNF-α) e a obesidade, permitindo definir mais claramente o papel dos adipócitos na saúde e na obesidade e como o TNF-α age sinalizando as moléculas neste processo, através de uma revisão bibliográfica. Os dados foram coletados em sites da internet e impressos de revistas científicas, abordando artigos científicos a partir de 1995. Diversos estudos apontam que a obesidade está caracterizada pelo aumento do tecido adiposo, hoje considerado um órgão endócrino ativo, que secreta uma variedade de substâncias metabólicas como hormônios, proteínas coagulantes e diversos fatores pró-inflamatório, incluindo o TNF-α. Este trabalho pretende mostrar a importância do TNF-α como uma citocina multifuncional com papel central de defesa a qual exerce várias atividades biológicas, bem como, o desenvolvimento e a expressão fenotípica da obesidade, pois age diretamente nos adipócitos, regulando o acúmulo de gordura e interferindo diretamente no metabolismo dos lipídios, inibindo a lipogênese e aumentando a lipólise nos adipócitos.
Referências
- Ahima, RS. e Flier, JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab, n. 11, p. 327-332, 2000.
- Bach, D.; e colaboradores. A. Effects of Type 2 Diabetes, Obesity, Weight Loss, and the Regulatory Role of Tumor Necrosis Factor and Interleukin-6. Diabetes, n. 54, p. 2685–2693, 2005.
- Boucher, J.; e colaboradores. Adipokine expression profile in adipocytes of different mouse models of obesity. Horm. Metab. Res, n. 37, v. 12, p. 761-767, 2005.
- Bouloumie, A.; e colaboradores. Role of macrophage tissue infiltration in metabolic diseases. Curr Opin Clin Nutr Metab Care, n. 8, p. 347-354, 2005.
- Bruun, J.M.; e colaboradores. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am. J. Physiol Endocrinol Metab., n. 285, p. E527-E533, 2003.
- Cancello, R.; e colaboradores. Reduction of macrophage infiltration and chemoattractant geneexpression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes, n. 54, p. 2277–2286, 2005.
- Candolfi, M.; e colaboradores. TNF-α_ Induces Apoptosis of Lactotropes from Female Rats. Endocrinology, n. 143, p. 3611–3617, 2002.
- Charriere, G.; e colaboradores. Preadipocyte conversion to macrophage. Evidence of plasticity. J. Biol. Chem, n. 278, p. 9850–9855, 2003.
- Citi e colaboradores. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res, n. 46, p. 2347–2355, 2005.
- Cousin, B.; e colaboradores. Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity. J. Cell. Physiol, n. 186, p. 380–386, 2001.
- De Pergola, G.; e Pannacciulli, N. Coagulation and fibrinolysis abnormalities in obesity. J. Endocrinol. Invest, n. 25, p. 899–904, 2002.
- Degawa-Yamauchi, M.; e colaboradores. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes. Res, v 13, n 4, p 662-669, 2005.
- Duffield, J. The inflammatory macrophage: a story of Jekyll and Hyde. Clin. Sci, n. 104, p. 27–28, 2003.
- Dzienis-Straczkowska, S.; e colaboradores. Soluble Tumor Necrosis Factor-alfa Receptors in Young Obese Subjects With Normal and Impaired Glucose Tolerance. Diabetes Care, n. 26, p. 875–880, 2003.
- Engelman, J.A.; e colaboradores. Tumor necrosis factor-α -mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. Mol Endocrinol, n. 14, p. 1557–1569, 2000.
- Benigni, F.; e colaboradores. The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle. The J. Clin. Investig, v. 106, n. 10, p. 1291-1300, 2000.
- Fain, JN.; Cheema, PS.; Bahouth, SW.; Lloyd-Hiler, M. Resistin release by human adipose tissue explants in primary culture. Biochem. Biophys. Res, n. 300, p. 674–678, 2003.
- Fernández-Real, JM.; e colaboradores. Polymorphism of the Tumor Factor-a Receptor 2 Gene With Obesity, Leptin Levels, Resistance in Young Subjects Diet-Treated Type 2 Diabetic. Diabetes Care, v. 23, n. 6, p. 831-837, 2000.
- Fonseca-Alaniz, M.H.; e colaboradores. O Tecido Adiposo Como Centro Regulador do Metabolismo. Arq. Brás. Endocrinol. Metab, v. 50, n. 2, p. 216-229, 2006.
- Fruebis J.; e colaboradores. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc.Natl. Acad. Sci, n. 98, p. 2005–2010, 2001.
- Winkler, G.; e colaboradores. Expression of tumor necrosis factor (TNF)-a protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-a, soluble serum TNF-receptor-2 concentrations and C-peptide level. Eur. J. Endocrinol, n. 149, p. 129–135, 2003.
- Good, M.; e colaboradores. TNF-α and TNF-α receptor expression and insulin sensitivity in human omental and subcutaneous adipose tissue influence of BMI and adipose distribution. Diab. Vasc. Dis. Res, v. 3, n. 1, p. 26-33, 2006.
- Greenberg, A.; e colaboradores. Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal related kinase pathway. J. Biol. Chem, n. 276, p. 454456–445461, 2001.
- Greenberg, S.A e Obin, M. Obesity and the role of adipose tissue in inflammation and metabolism . Am. J. Clin. Nutr, n. 83, p. 461S–465S, 2006.
- Gregorio, G.B.D.I.; e colaboradores. Expression of CD68 and Macrophage Chemoattractant Protein-1 Genes in Human Adipose and Muscle Tissues Association With Cytokine Expression, Insulin Resistance, and Reduction by Pioglitazone. Diabetes, n. 54, p. 2305-2313, 2005.
- Gwozdziewiczová, S. e colaboradores. TNF-α in the development of insulin resistance and other disorders. Biomed. Pap. Med, v. 149, n.1, p. 109-117, 2005.
- Hamminga, E.A.; e colaboradores. Chronic inflammation in psoriasis and obesity: Implications for therapy. Med. Hypotheses, v. 67, n. 4; p. 768-773 , 2006.
- Hara, K.; Boutin, P.; Mori, Y. e colaboradores. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes, n. 51, p. 536–540, 2002.
- Hauner, H. Secretory factors from human adipose tissue and their funcionale role. Proc. Nutrition Sociaty, v. 64, n. 2, p. 163-169, 2005.
- Hotta, K.; Funahashi, T.; Arita, Y. e colaboradores. Plasma concentrations of a novel, IN Metabolic Syndrome, 2005.
- James, M.J.; Gibson, R.A; Cleland, L.G. Supplements Dietary polyunsaturated fatty acids and inflammatory mediator production1,2 . Am. J. Clin. Nut, v. 71, n. 1, p. 343-348, 2000.
- Kelley, D.E. e Mandarino, L.J: Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes, n. 49, p. 677–683, 2000.
- Kern, P.A.; e colaboradores. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab, n. 280, p. E745–E751, 2001.
- Kim, E.Y.; e colaboradores. TNF receptor type 2 (p75) functions as a costimulator for antigen-driven T cell responses in vivo. J. Immunol, v. 15, n. 176, p. 1026-35, 2006.
- Kissebah, A.H.; e colaboradores. Quantitative trait locion chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc. Natl. Acad. Sci, n. 97, p. 14478–1483, 2000.
- Kougias, P. e colaboradores. Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. J. Surg. Res, v 126, n 1, p 121-129, 2005.
- Kreier, F.; e colaboradores. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat – functional implications. J. Clin. Invest, n. 110, p. 1243-1250, 2002.
- Kullo, I.J.; Hensrud, D.D.; Allison, T.G. Comparison of numbers of circulating blood monocytes in men grouped by body mass index (<25, 25 to <30, > or = 30). Am. J. Cardiol, n. 89, p. 1441–1443, 2002.
- Lin, Y.; e colaboradores. The Lipopolysaccharide-activated Toll-like Receptor (TLR)-4 Induces Synthesis of the Closely Related Receptor TLR-2 in Adipocytes. J. Biol. Chem, n. 275, p. 24255-24263, 2000.
- Loskutoff, D.J.; e colaboradores. The fat mouse: A powerful genetic model to study alterations in hemostatic gene expression in obesity. I. N. Front. Vasc. Biol. Thromb. Hem, p. 151-160, 2000.
- Lyon, C.J.; Law, R.E., Hsueh, W.A. Minireview: Adiposity, Inflammation, and Atherogenesis. Endocrinol, v. 6, n. 144, p. 2195–2200, 2003.
- Matsuda, M, e colaboradores. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J. Biol. Chem, n. 277, p. 37487-37491, 2002.
- Old, L. Tumoral Necrosis Factor (TNF). Science, n. 230, p. 630-633, 1985.
- Ouchi, N.; Kihara, S.; Arita, Y. e colaboradores. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation, n. 103, p. 1057–1063, 2001.
- Pandey, M.; Loskutoff, D.J.; Samad, F. Molecular mechanisms of tumor necrosis factor-α-mediated plasminogen activator inhibitor-1 expression in adipocytes. FASEB J., article 10.1096/fj.04-3459fje, 2005.
- Pausova, Z.; Deslauriers,B.; Gaudet, D. Tremblay, J.; Kotchen, T.A.; Larochelle, P.; Cowley, A.W.; Hamet, P. Role of Tumor Necrosis Factor-a Gene Locus in Obesity and Obesity-Associated Hypertension in French Canadians. Hypertension, n. 36, p. 14-19, 2000.
- Pénicaud, L. e colaboradores. The autonomic nervous system, adipose tissue plasticity, and energy balance. Nutrition, n. 16, p. 903-908, 2000.
- Pietiläinen, K.H.; e colaboradores. Acquired obesity increases cd68 and TNF-α and decreases adiponectin gene expression in adipose tissue. A study in monozygotic twins. J. Clin. Endocrin. Metab, n. 10, p. 01-22, 2006.
- Pinheiro, A.R.O.; Freitas, S.F.T. de; Corso, A.C.T. Uma abordagem epidemiológica da obesidade. Rev. Nutr. Campinas, v. 17, n. 4, p. 523-533, 2004.
- Qi, C. e Pekala, P. Minerevies: Tumoral Necrose Factor-α Induced Insulin Resistenc Adipocytes. SEBM, n. 223, p. 128-135, 2000.
- Rajala, M.W. e Scherer, P.E. Minireview: The Adipocyte at the Crossroads of Energy Homeostasis, Inflammation, and Atherosclero-sis. Endocrinol, v. 144, n. 9, p. 3765–3773, 2003.
- Ronti ,T.; Lupattelli, G., Mannarino, E. The endocrine function of adipose tissue: an update. Clin. Endocrinol, v. 64, n. 4, p. 355-365, 2006.
- Ross, S.E.; e colaboradores. Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor alpha in adipocyte metabolism. Mol. Cell. Biol, n. 22, p. 5989–5999, 2002.
- Shirai, T.; e colaboradores. Cloning and expression in Esccherichia coli of gene for human tumour necrose factor. Nature, n. 313, p803-806, 1985.
- Skurk, T.; e colaboradores. Production and Release of Macrophage Migration Inhibitory Factor from Human Adipocytes. Endocrinol, n. 146, p. 1006–1011, 2005.
- Suganami, T.; Nishida, J.; Ogawa, Y.A. Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes Role of Free Fatty Acids and Tumor Necrosis Factor . Arterioscler. Thromb. Vasc. Biol, n. 25, p. 2062-2068, 2005.
- Takahashi, K.; e colaboradores. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem, n. 278, p. 46654–46660, 2003.
- Takahashi, M.; e colaboradores. Genomic structure and mutations in adipose-specific gene, adiponectina. Int. J. Obes. Relat. Metab. Disord, n. 24, p. 861-868, 2000.
- Tomas, E.; e colaboradores. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl. Acad. Sci, n. 99, p. 16309–16313, 2002.
- Trujillo, M.E.; e colaboradores. Tumor Necrosis Factor αand Glucocorticoid Synergistically Increase Leptin Production in Human Adipose Tissue – Role for p38 MAPK. J. Clin. Endocrin. Metab, n. 10, p. 1210-1237, 2006.
- Turcotte, L.P.; e colaboradores. Increased fatty acid uptake and altered fatty acid metabolism in insulin-resistant muscle of obese Zucker rats. Diabetes, n. 50, p. 1389–1396, 2001.
- Van Dielen, F.M.H.; e colaboradores. Macrophage Inhibitory Factor, Plasminogen Activator Inhibitor-1, Other Acute Phase Proteins, and Inflammatory Mediators Normalize as a Result of Weight Loss in Morbidly Obese Subjects Treated with Gastric Restrictive Surgery. J. Clin. Endocrinol. Metab, v. 89, p. 4062–4068, 2004.
- Warne, J.P. Tumour necrosis factor alpha: a key regulator of adipose tissue mass. J. Endocrinol, n. 177, p. 351-355, 2003.
- Weisberg, S.D.; e colaboradores. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest, n. 112, p. 1796–1808, 2003.
- Weisberg, S.P.; Mccann, D.; Desai, M.; Rosenbaum, M.; Leibel, R.L.; Ferrante, A.W. Jr. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest, n. 112, p. 1796–1808, 2003.
- Winkler, G.; e colaboradores. Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level. Eur. J. Endocrinol, v. 149, n. 2, p. 129-135, 2003.
- World Health Organization (WHO). Fact sheet: obesity and overweight. Internet: http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/ (aceso 18 de março de 2006).
- Wu, X.; e colaboradores. Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes, n. 52, p. 1355-1363, 2003.
- Xu, H.; e colaboradores. Exclusive Action of Transmembrane TNF-α in Adipose Tissue Leads to Reduced Adipose Mass and Local But Not Systemic Insulin Resistance. Endocrinol, v. 143, n. 4, p1502–1511, 2002.
- Xu, H.; e colaboradores. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest, n. 112, p. 1821–1830, 2003.
- Xu,; H. e colaboradores. Altered Tumor Necrosis Factor-α_ (TNF-α) Processing in Adipocytes and Increased Expression of Transmembrane TNF-α in Obesity. Diabets, v. 51, p. 1876-1883, 2002.
- Yamauchi, T.; e colaboradores. The fat-derived hormone adiponectin reverses adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler. Thromb. Vasc. Biol, n. 20, p. 1595–1599, 2000.
- Yang, R.Z.; e colaboradores. Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications. PLos. Med, v. 3, n. 6, p 287-298, 2006.
- Yokota, T.; e colaboradores. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, n 96, p. 1723-1732, 2000.
- Zhang, H.H.; e colaboradores. Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes, n. 51, p. 2929–2935, 2002.
Autores que publicam neste periódico concordam com os seguintes termos:
- Autores mantém os direitos autorais e concedem ao periódico o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Creative Commons Attribution License BY-NC que permitindo o compartilhamento do trabalho com reconhecimento da autoria do trabalho e publicação inicial neste periódico.
- Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada neste periódico (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial neste periódico.
- Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citaçao do trabalho publicado (Veja O Efeito do Acesso Livre).
