Obesidade: uma abordagem inflamatória e microbiana

Autores

  • Diego da Silva Lutkemeyer Universidade de São Paulo, Faculdade de Medicina - São Paulo, SP
  • Mariana Abrantes do Amaral Universidade de São Paulo, Instituto de Ciências Biomédicas - São Paulo, SP
  • Nathalia Hiromi Ishida Assunção Universidade de São Paulo, Instituto de Ciências Biomédicas - São Paulo, SP
  • Nathália Franchon Marques Tejada Universidade de São Paulo, Faculdade de Medicina - São Paulo, SP
  • Niels Olsen Saraiva Camara Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Imunologia - São Paulo, SP

DOI:

https://doi.org/10.34019/1982-8047.2018.v44.13963

Palavras-chave:

Imunologia, Obesidade, Inflamação, Microbiota

Resumo

A obesidade está intimamente ligada ao estado inflamatório, sendo considerada uma patologia metabólica complexa. Dietas hipercalóricas alteram a composição da microbiota intestinal, sendo a mudança da proporção de bactérias dos filos Bacteroidetes e Firmicutes uma das consequências mais conhecidas.  Essa mudança determina a produção de metabólitos específicos do sistema imune, induzindo estado inflamatório responsável pelo agravamento de uma série de doenças. A dieta hipercalórica representa um fator de risco para a obesidade e para o diabetes mellitus, doenças interligadas pelo conceito de lipotoxicidade, e o estado inflamatório também contribui para o aparecimento e para a progressão de doenças cardiovasculares. Com esse artigo, objetivamos estudar a obesidade pela perspectiva imunológica e microbiológica, abordando as consequências de dietas hipercalóricas sobre o estado inflamatório e a sobre a microbiota. Ademais, associar a mudança no microbioma a doenças prevalentes como o diabetes mellitus e as doenças cardiovasculares, apontando abordagens terapêuticas potenciais.

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Referências

ABT, M. C.; ARTIS, D. The intestinal microbiota in health and disease: the influence of microbial products on immune cell homeostasis. Current Opinion in Gastroenterology, v. 25, n. 6, p. 496, feb. 2009.

AJSLEV, T. A. et al. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. International Journal of Obesity, v. 35, p. 522–529, abr. 2011

BAMGBOLA, O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Therapeutic Advances in Endocrinology and Metabolism, v. 7, n. 3, p. 110-127, jun. 2017.

BÄCKHED, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences, v. 101, n. 44, p. 15718-15723, nov. 2004.

BÄCKHED, F. et al. Host-bacterial mutualism in the human intestine. Science, v. 307, n. 5717, p. 1915-1920, mar. 2005.

BOULOUMIÉ, A. et al. Role of macrophage tissue infiltration in metabolic diseases. Current Opinion in Clinical Nutrition & Metabolic Care, v. 8, n. 4, p. 347-54, jul. 2005.

CASTOLDI, A. et al. Dectin-1 activation exacerbates obesity and insulin resistance in the absence of myd88. Cell reports, v. 19, n. 11, p. 2272-2288, jun. 2017.

CARBONE, F. et al. Metabolic control of immune tolerance in health and autoimmunity. Seminars in Immunology, v. 28, n. 5, p. 491-504, oct. 2016.

CINTI, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. Journal Lipid Research, v. 46, n. 11, p. 2347-55, nov. 2005.

DELZENNE, N. M. et al. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nature Reviews Endocrinology, v. 7, p. 639–646, aug. 2011

DIABETES.ORG. Diretrizes sociedade brasileira de diabetes 2017-2018. Disponível em: <https://www.diabetes.org.br/profissionais/images/2017/diretrizes/diretrizes-sbd-2017-2018.pdf>. Acesso em: 08 dez. 2018.

DIBAISE, J. K. et al. Gut microbiota and its possible relationship with obesity. Mayo Clinic Proceedings, v. 83, n. 4, p. 460-469, apr. 2008.

DUNCAN, S. H. et al. Human colonic microbiota associated with diet, obesity and weight loss. International Journal of Obesity, v. 32, n. 11, p. 1720, nov. 2008.

DURÁN, W. N. The double-edge sword of TNF-alpha in ischemia-reperfusion injury. American Journal of Physiology-Endocrinology and Metabolism, v. 295, n. 6, p. H221-222, oct. 2008.

FERRARI, R. The role of TNF in cardiovascular disease. Pharmacological Research, v. 40, n. 2, p. 97-105, aug. 1999.

FREELAND, K. R. et al. Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide yy, ghrelin, adiponectin and tumour necrosis factor-alpha. The British Journal of Nutrition, v. 103, n. 3, p. 460-466, feb. 2010.

FRUHBECK, G. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes, v. 48, n. 4, p. 903-908, apr. 1999.

GRAHAM, C.; MULLEN, A.; WHELAN, K. Obesity and the gastrointestinal microbioma: a review of associations and mechanisms. Nutrition Reviews, v. 73, n. 6, p. 376-385, jun. 2015.

GROOT, P. F. de et al. Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes, v. 8, n. 3, p. 253–267, fev. 2017.

HOOPER, L. V. et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science, v. 291, n. 5505, p. 881-884, feb. 2001.

HOTAMISLIGIL, G. S. et al. Irs-i-mediated inhibition of insulin receptor tyrosine kinase activity in tnf-a- and obesity-induced insulin resistance. Science, v. 271, n. 5249, p. 665-670, feb. 1996.

GREGOR, M. F.; HOTAMISLIGILl, G. S. Inflammatory mechanisms in obesity. Annual reviews, v. 29, p. 415-445, apr. 2011.

HUBER S. Tumor necrosis factor-alpha promotes myocarditis in female mice infected with coxsackievirus B3 through upregulation of CD1d on hematopoietic cells. Viral Immunology, v. 23, n. 1, p. 79-86, feb. 2010.

IGLAY, K. et al. Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus. Current Medical Research and Opinion, v. 32, n. 7, p. 1243-1252, jul. 2016.

KADOOKA, Y. et al. Regulation of abdominal adiposity by probiotics (lactobacillus gasseri sbt2055) in adults with obese tendencies in a randomized controlled trial. European Journal of Clinical Nutrition, v. 64, n. 6, p. 636–643, mar. 2010.

KANDA, T., TAKAHASHI, T. Interleukin-6 and cardiovascular diseases. Japanese Heart Journal, v. 45, n. 2, p. 183-193, mar. 2004.

KELLY, T. et al. Global burden of obesity in 2005 and projections to 2030. International Journal of Obesity, v. 32, n. 9, p. 1431-7, sep. 2008.

LEMBO, G. et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes, v. 49, n. 2, p. 293-297, feb. 2000.

LEY, R. E. et al. Microbial ecology: human gut microbes associated with obesity. Nature, v. 444, n. 7122, p. 1022, dec. 2006.

LIEBER, A. et al. Effect of oligofructose supplementation on body weight in overweight and obese children: a randomised, double-blind, placebo-controlled trial. British Journal of Nutrition, v. 112, n. 12, p. 2068-2074, dec. 2014.

LO, J. et al. Effects of tnf-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome. American Journal of Physiology-Endocrinology and Metabolism, v. 293, n. 1, p. 102-109, jul. 2007.

LOLMÈDE, K. et al. Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes. International Journal of Obesity, v. 27, n. 10, p. 1187-95, oct. 2003.

LOUIS, P.; HOLD, G. L.; LINT, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nature Reviews Microbiology, v. 12, n. 10, p. 661, nov. 2014.

LUMENG, C. N.; BODZIN, J. L.; SALTIEL, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. The Journal of Clinical Investigation, v. 117, n. 1, p. 175-84, jan. 2007.

MACGOWAN, G. A. et al. Circulating interleukin-6 in severe heart failure. The American Journal of Cardiology, v. 79, n. 8, p. 1128-1131, apr. 1997.

MCGOWN, C.; BIRERDINC, A.; YOUNOSSI, Z. M. Adipose tissue as an endocrine organ. Clinics in Liver Disease, v. 18, n. 1, p. 41-58, feb. 2014.

MCFALL-NGAI, M. et al. Animals in a bacterial world, a new imperative for the life sciences. Proceedings of the National Academy of Sciences, v. 110, n. 9, p. 3229-3236, feb. 2013.

NAKAJIMA, A. et al. The short chain fatty acid receptor gpr43 regulates inflammatory signals in adipose tissue m2-type macrophages. Plos One, v. 12, n. 7, p. 1-18, jul. 2017.

NICOLUCCI, A. C. et al. Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology, v. 153, n. 3, p. 711-722, sep. 2017.

NIGRO, E. et al. New insight into adiponectin role in obesity and obesity-related diseases. BioMed Research International, v. 2014, jul. 2014.

NIIJIMA, A. Afferent signals from leptin sensors in the white adipose tissue of the epididymis, and their reflex effect in the rat. Journal of the Autonomic Nervous System, v. 73, n. 1, p. 19-25, aug. 1998.

NIIJIMA, A. Reflex effects from leptin sensors in the white adipose tissue of the epididymis to the efferent activity of the sympathetic and vagus nerve in the rat. Neuroscience Letters, v. 262, n. 2, p. 125-128, mar. 1999.

OLEFSKY, J. M.; GLASS, C. K. Macrophages, inflammation, and insulin resistance. Annual Review of Physiology, v. 72, p. 219-46, mar. 2010..

OUCHI, N.; WALSH, K. Adiponectin as an anti-inflammatory factor. Clinica Chimica Acta, v. 380, n. 1-2, p. 24-30, may. 2007.

OUCHI, N. et al. Adipokines in inflammation and metabolic disease. Nature Reviews Immunology, v. 11, n. 2, p. 85-97, feb. 2011.

PAHWA, R. et al. Gut microbiome and inflammation: a study of diabetic inflammasome-knockout mice. Journal of Diabetes Research, v. 2017, p. 1-5, dec. 2017.

PANTALONE, K. M. et al. Prevalence and recognition of obesity and its associated comorbidities: cross-sectional analysis of electronic health record data from a large us integrated health system. Bmj Open, v. 7, n. 11, p. 1-9, out. 2018.

PERRY, R. J. et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature, v. 534, p. 213–217, jun. 2016.

PETRIC, B. G. et al. Targeted activation of c-Jun N-terminal kinase in vivo induces restrictive cardiomyopathy and conduction defects. Journal of Biological Chemistry, v. 279, n. 15, p. 15330-15338, apr. 2004.

POPKO, K. et al. Proinflammatory cytokines Il-6 and TNF-α and the development of inflammation in obese subjects. European Journal of Medical Research, v. 15, n. 2, p. 120, nov. 2010.

REIJNDERS, D. et al. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: a randomized double-blind placebo-controlled trial. Cell Metabolism, v. 24, n. 1, p. 63-74, jul. 2016.

SAAD, J. A. et al. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology, v. 31, n. 4, p. 283-293, jul. 2016.

SANCHEZ, M. et al. Effect of lactobacillus rhamnosus cgmcc1.3724 supplementation on weight loss and maintenance in obese men and women. British Journal of Nutrition, v. 111, n. 8, p. 1507-1519, apr. 2014.

SCHREZENMEIR, J.; VRESE, M. D. Probiotics, prebiotics, and synbiotics—approaching a definition. The American Journal of Clinical Nutrition, v. 73, n. 2,p. 361-364, feb. 2001.

SHOKOLENKO, I. et al. Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Research, v. 37, n. 8, p. 2539-48, may. 2009.

STANLEY, T. L. et al. Tnf-α antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. The Journal of Clinic Endocrinology and Metabolism, v. 96, n. 1, p. 146-150, jan. 2011.

SHIBATA, R.; OUCH, N.; MUROHARA, T. Adiponectin and cardiovascular disease. Circulation Journal, p. 0902260284-0902260284, mar. 2009.

TANIDA, M. et al. Leptin injection into white adipose tissue elevates renal sympathetic nerve activity dosedependently through the afferent nerves pathway in rats. Neuroscience Letters, v. 293, n. 2, p. 107-110, oct. 2000.

TAUBE, A. et al. Inflammation and metabolic dysfunction: links to cardiovascular diseases. American Journal of Physiology-Heart and Circulatory Physiology, v. 302, n. 11, p. H2148-2165, mar. 2012.

THALER, J. P. et al. Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes, v. 62, p. 2629-2634, apr. 2013.

TRAYHURN, P.; WOOD, I. S. Adipokines: inflammation and the pleiotropic role of white adipose tissue. British Journal of Nutrition, v. 92, n. 3, p. 347-55, sep. 2004.

TILG, H.; MOSCHEN, A. R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nature Reviews Immunology, v. 6, n. 10, p. 772-83, oct. 2006.

VAN DEN ELSEN, L. W. et al. Embracing the gut microbiota: the new frontier for inflammatory and infectious diseases. Clinical & Translational Immunology, v. 6, n. 1, p. e125, jan. 2017.

VRIEZE, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, v. 143, n. 4, p. 913-916, oct. 2012.

WASCHER, T. C. et al. Chronic tnf-α neutralization does not improve insulin resistance or endothelial function in “healthy” men with metabolic syndrome. Molecular Medicine, v. 17, n. 4, p. 189-193, mar. 2011.

WEIL, B. R. et al. Enhanced endothelin-1 system activity with overweight and obesity. American Journal of Physiology-Heart and Circulatory Physiology, v. 301, n. 3, p. H689-695, sep. 2011.

WILDING, J. Thiazolidinediones, insulin resistance and obesity: finding a balance. The International Journal of Clinical Practice, v. 60, n. 10, p. 1272-1280, sep. 2006.

WOLLERT, K. C.; DREXLER, H. The role of interleukin-6 in the failing heart. Heart Failure Reviews, v. 6, n. 2, p. 95-103, mar. 2001.

WELLEN, K. E.; HOTAMISLIGIL, G. S. Obesity-induced inflammatory changes in adipose tissue. The Journal of Clinical Investigation, v. 112, n. 12, p. 1785-8, dec. 2003.

YE, J. Mechanisms of insulin resistance in obesity. Frontiers of Medicine, v. 7, n. 1, p. 14-24, mar. 2013.

YOSHIMOTO, S. et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature, v. 499, n. 7456, p. 97, jul. 2013.

ZARRATI, M. et al. Effects of probiotic yogurt on fat distribution and gene expression of proinflammatory factors in peripheral blood mononuclear cells in overweight and obese people with or without weight-loss diet. European Journal of Clinical Nutrition, v. 33, n. 6, p. 417–425, jul. 2014.

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Publicado

2019-04-04

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1.
Lutkemeyer D da S, do Amaral MA, Ishida Assunção NH, Marques Tejada NF, Saraiva Camara NO. Obesidade: uma abordagem inflamatória e microbiana. HU Rev [Internet]. 4º de abril de 2019 [citado 29º de março de 2024];44(2):221-9. Disponível em: https://periodicos.ufjf.br/index.php/hurevista/article/view/13963

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