Low-Grade Inflammation, Obesity, and Diabetes

Abstract

Obesity and its comorbidities are closely related to the inflammatory environment created by expanded adipose tissue. Several mechanisms trigger inflammation in adipose tissue, including excess fatty acids, hypoxia, and activation of the inflammasome. Inflammation is characterized by the abundance of immune cells, particularly M1 macrophages and T lymphocytes, which have increased secretion of proinflammatory cytokines that act to perpetuate systemic inflammation and induce insulin resistance. The gut microbiota is also involved in obesity-induced inflammation via LPS-related endotoxemia that induces cytokine secretion and insulin resistance. Innate lymphoid type 2 cells, regulatory T cells, and interleukine (IL)-10 counteract the inflammation and insulin resistance, establishing classical or metabolically healthy obesity.

This is a preview of subscription content, log in to check access.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    de Heredia FP, Gomez-Martinez S, Marcos A. Obesity, inflammation and the immune system. Proc Nutr Soc. 2012;71:332–8.

    PubMed  Article  Google Scholar 

  2. 2.

    Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  3. 3.

    Fain, J.N. Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review. Mediators Inflamm 2010, 513948.

  4. 4.

    van Greevenbroek MM, Schalkwijk CG, Stehouwer CD. Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences. Neth J Med. 2013;71:174–87.

    PubMed  Google Scholar 

  5. 5.

    Bigornia SJ, Farb MG, Mott MM, Hess DT, Carmine B, Fiscale A, et al. Relation of depot-specific adipose inflammation to insulin resistance in human obesity. Nutr Diabetes. 2012;2:e30.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  6. 6.

    Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008;28:1039–49.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Marinou K, Tousoulis D, Antonopoulos AS, Stefanadi E, Stefanadis C. Obesity and cardiovascular disease: from pathophysiology to risk stratification. Int J Cardiol. 2010;138:3–8.

    PubMed  Article  Google Scholar 

  8. 8.

    Primeau V, Coderre L, Karelis AD, Brochu M, Lavoie ME, Messier V, et al. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes (Lond). 2011;35:971–81.

    CAS  Article  Google Scholar 

  9. 9.

    Zeyda M, Stulnig TM. Obesity, inflammation, and insulin resistance–a mini-review. Gerontology. 2009;55:379–86.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Girard J, Lafontan M. Impact of visceral adipose tissue on liver metabolism and insulin resistance. Part II: Visceral adipose tissue production and liver metabolism. Diabetes Metab. 2008;34:439–45.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9:191–200.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  12. 12.

    Li ZY, Wang P, Miao CY. Adipokines in inflammation, insulin resistance and cardiovascular disease. Clin Exp Pharmacol Physiol. 2011;38:888–96.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Lemoine AY, Ledoux S, Larger E. Adipose tissue angiogenesis in obesity. Thromb Haemost. 2013;110.

  14. 14.

    Gualillo O, Gonzalez-Juanatey JR, Lago F. The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. Trends Cardiovasc Med. 2007;17:275–83.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Pujanek M, Bronisz A, Malecki P, Junik R. Pathomechanisms of the development of obesity in some endocrinopathies - an overview. Endokrynol Pol. 2013;64:150–5.

    CAS  PubMed  Google Scholar 

  16. 16.

    Leal Vde O, Mafra D. Adipokines in obesity. Clin Chim Acta. 2013;419:87–94.

    PubMed  Article  Google Scholar 

  17. 17.

    Jung CH, Kim MS. Molecular mechanisms of central leptin resistance in obesity. Arch Pharm Res. 2013;36:201–7.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    D’Ippolito S, Tersigni C, Scambia G, Di Simone N. Adipokines, an adipose tissue and placental product with biological functions during pregnancy. Biofactors. 2012;38:14–23.

    PubMed  Article  Google Scholar 

  19. 19.

    Ye J, McGuinness OP. Inflammation during obesity is not all bad: evidence from animal and human studies. Am J Physiol Endocrinol Metab. 2013;304:E466–77.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  20. 20.

    Vazquez-Vela ME, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res. 2008;39:715–28.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Yadav A, Kataria MA, Saini V. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013;417:80–4.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Lenz A, Diamond Jr FB. Obesity: the hormonal milieu. Curr Opin Endocrinol Diabetes Obes. 2008;15:9–20.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Yamauchi T, Kadowaki T. Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes (Lond). 2008;32 Suppl 7:S13–8.

    CAS  Article  Google Scholar 

  24. 24.

    Lago F, Gomez R, Gomez-Reino JJ, Dieguez C, Gualillo O. Adipokines as novel modulators of lipid metabolism. Trends Biochem Sci. 2009;34:500–10.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Pereira SS, Alvarez-Leite JI. Adipokines: biological functions and metabolically healthy obese profile. J Recept Ligand Channel Res. 2014;7:1–11.

    Google Scholar 

  26. 26.

    Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316:129–39.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Zou C, Shao J. Role of adipocytokines in obesity-associated insulin resistance. J Nutr Biochem. 2008;19:277–86.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314:1–16.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Balistreri CR, Caruso C, Candore G. The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediat Inflamm. 2010;2010:802078.

    Article  Google Scholar 

  30. 30.

    Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–77.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  31. 31.

    Hermsdorff HH, Angeles Zulet M, Bressan J, Alfredo Martinez J. Effect of diet on the low-grade and chronic inflammation associated with obesity and metabolic syndrome. Endocrinol Nutr. 2008;55:409–19.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Bray GA, Clearfield MB, Fintel DJ, Nelinson DS. Overweight and obesity: the pathogenesis of cardiometabolic risk. Clin Cornerstone. 2009;9:30–40. discussion 41–32.

    PubMed  Article  Google Scholar 

  33. 33.

    Lee J. Adipose tissue macrophages in the development of obesity-induced inflammation, insulin resistance and type 2 Diabetes. Arch Pharm Res. 2013;36:208–22.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  34. 34.

    Sun S, Ji Y, Kersten S, Qi L. Mechanisms of inflammatory responses in obese adipose tissue. Annu Rev Nutr. 2012;32:261–86.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  35. 35.

    Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116:1494–505.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  36. 36.

    Itoh M, Suganami T, Hachiya R, Ogawa Y. Adipose tissue remodeling as homeostatic inflammation. Int J Inflamm. 2011;2011:720926.

    Article  Google Scholar 

  37. 37.

    Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930–9.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  38. 38.

    Gotoh K, Inoue M, Masaki T, Chiba S, Shimasaki T, Ando H, et al. A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver. Diabetes. 2012;61:1994–2003.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  39. 39.

    Chen W, Konkel JE. TGF-beta and ‘adaptive’ Foxp3(+) regulatory T cells. J Mol Cell Biol. 2010;2:30–6.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  40. 40.

    Chen X, Oppenheim JJ. Resolving the identity myth: key markers of functional CD4 + FoxP3+ regulatory T cells. Int Immunopharmacol. 2011;11:1489–96.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  41. 41.

    Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, et al. Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling. Cell Metab. 2011;14:67–79.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  42. 42.

    Tan CK, Chong HC, Tan EH, Tan NS. Getting ‘Smad’ about obesity and diabetes. Nutr Diabetes. 2012;2:e29.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  43. 43.

    Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011;12:722–34.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Chmelar J, Chung KJ, Chavakis T. The role of innate immune cells in obese adipose tissue inflammation and development of insulin resistance. Thromb Haemost. 2013;109:399–406.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Kalupahana NS, Moustaid-Moussa N, Claycombe KJ. Immunity as a link between obesity and insulin resistance. Mol Aspects Med. 2012;33:26–34.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Harford KA, Reynolds CM, McGillicuddy FC, Roche HM. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc. 2011;70:408–17.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347–55.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Lolmede K, Duffaut C, Zakaroff-Girard A, Bouloumie A. Immune cells in adipose tissue: key players in metabolic disorders. Diabetes Metab. 2011;37:283–90.

    CAS  PubMed  Article  Google Scholar 

  49. 49.••

    Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes. 2012;61:2238–47. This paper shows for the first time the presence of specific DCs in adipose tissue in mouse and human obesity.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  50. 50.

    Patel PS, Buras ED, Balasubramanyam A. The role of the immune system in obesity and insulin resistance. J Obes. 2013;2013:616193.

    PubMed Central  PubMed  Google Scholar 

  51. 51.••

    Chen Y, Tian J, Tian X, Tang X, Rui K, Tong J, et al. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS ONE. 2014;9:e92450. The results of this study indicates the existence of CD11c + DCs in adipose tissue, which displays an immature phenotype but possessing pro-inflammatory function.

    PubMed Central  PubMed  Article  Google Scholar 

  52. 52.••

    Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med. 2012;18:1407–12. The authors show that treatment of hepatocytes with neutrophil elastase causes insulin resistance and that deletion of neutrophil elastase in obese mice reduce inflammation.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  53. 53.

    Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332:243–7.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  54. 54.

    Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013;210:535–49.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  55. 55.

    Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2010;463:540–4.

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15:921–9.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  57. 57.

    Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, et al. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature. 2012;486:549–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  58. 58.

    Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, Stanzl U, et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes. 2011;60:2954–62.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  59. 59.

    Cipolletta D, Kolodin D, Benoist C, Mathis D. Tissular T(regs): a unique population of adipose-tissue-resident Foxp3 + CD4+ T cells that impacts organismal metabolism. Semin Immunol. 2011;23:431–7.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Deiuliis J, Shah Z, Shah N, Needleman B, Mikami D, Narula V, et al. Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers. PLoS ONE. 2011;6:e16376.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  61. 61.

    Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJ, John S, Taams LS. CD4 + CD25 + Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci U S A. 2007;104:19446–51.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  62. 62.

    Chen, X., Wu, Y., and Wang, L. Fat-resident Tregs: an emerging guard protecting from obesity-associated metabolic disorders. Obes Rev. 2013;14:568–78.

  63. 63.

    Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between Adipocytes and Immune Cells in Adipose Tissue Inflammation and Metabolic Dysregulation in Obesity. Mol Cells. 2014;37(5):365–71.

    PubMed Central  PubMed  Article  Google Scholar 

  64. 64.

    Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15:914–20.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Kotas ME, Lee HY, Gillum MP, Annicelli C, Guigni BA, Shulman GI, et al. Impact of CD1d deficiency on metabolism. PLoS ONE. 2011;6:e25478.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  66. 66.

    Mantell BS, Stefanovic-Racic M, Yang X, Dedousis N, Sipula IJ, O’Doherty RM. Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS ONE. 2011;6:e19831.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  67. 67.

    Nishimura, S., Manabe, I., Takaki, S., Nagasaki, M., Otsu, M., Yamashita, H., Sugita, J., Yoshimura, K., Eto, K., Komuro, I., et al. (2013). Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation. Cell Metab.

  68. 68.

    Liu J, Divoux A, Sun J, Zhang J, Clément K, Glickman JN, et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med. 2009;15:940–5.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  69. 69.

    Robbins GR, Wen H, Ting JP. Inflammasomes and Metabolic Disorders: Old Genes in Modern Diseases. Mol Cell. 2014;54:297–308.

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Wieser V, Moschen AR, Tilg H. Inflammation, cytokines and insulin resistance: a clinical perspective. Arch Immunol Ther Exp (Warsz). 2013;61:119–25.

    CAS  Article  Google Scholar 

  71. 71.

    Skeldon AM, Faraj M, Saleh M. Caspases and inflammasomes in metabolic inflammation. Immunol Cell Biol. 2014;92:304–13.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Jin C, Flavell RA. Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol. 2013;132:287–94.

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011;108:15324–9.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  74. 74.

    Koenen TB, Stienstra R, van Tits LJ, Joosten LA, van Velzen JF, Hijmans A, et al. The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology. 2011;152:3769–78.

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17:179–88.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  76. 76.••

    Tilg, H., and Moschen, AR.Microbiota and diabetes: an evolving relationship. Gut. 2014. The paper reviews the role of the microbiota in diabetes and provide new aspects regarding its pathophysiological relevance.

  77. 77.

    Remely M, Aumueller E, Jahn D, Hippe B, Brath H, Haslberger AG. Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity. Benef Microbes. 2014;5:33–43.

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Moreno-Indias I, Cardona F, Tinahones FJ, Queipo-Ortuño MI. Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus. Front Microbiol. 2014;5:190.

    PubMed Central  PubMed  Article  Google Scholar 

  79. 79.

    Kemp DM. Does chronic low-grade endotoxemia define susceptibility of obese humans to insulin resistance via dietary effects on gut microbiota? Adipocyte. 2013;2:188–90.

    PubMed Central  PubMed  Article  Google Scholar 

  80. 80.

    Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94:58–65.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  81. 81.

    Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  82. 82.

    Mai V, McCrary QM, Sinha R, Glei M. Associations between dietary habits and body mass index with gut microbiota composition and fecal water genotoxicity: an observational study in African American and Caucasian American volunteers. Nutr J. 2009;8:49.

    PubMed Central  PubMed  Article  Google Scholar 

  83. 83.

    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Mehta NN, Heffron SP, Patel PN, Ferguson J, Shah RD, Hinkle CC, et al. A human model of inflammatory cardio-metabolic dysfunction; a double blind placebo-controlled crossover trial. J Transl Med. 2012;10:124.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  85. 85.

    Mehta NN, McGillicuddy FC, Anderson PD, Hinkle CC, Shah R, Pruscino L, et al. Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes. 2010;59:172–81.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  86. 86.

    Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–23.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  87. 87.

    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

    PubMed  Article  Google Scholar 

  88. 88.

    Lee MJ, Wu Y, Fried SK. Adipose tissue remodeling in pathophysiology of obesity. Curr Opin Clin Nutr Metab Care. 2010;13:371–6.

    PubMed Central  PubMed  Article  Google Scholar 

  89. 89.

    Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Investig. 2011;121:2094–101.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  90. 90.

    Bluher M. The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals. Curr Opin Lipidol. 2010;21:38–43.

    PubMed  Article  Google Scholar 

  91. 91.

    Pataky Z, Bobbioni-Harsch E, Golay A. Open questions about metabolically normal obesity. Int J Obes (Lond). 2010;34 Suppl 2:S18–23.

    Article  Google Scholar 

  92. 92.

    Esser N, L’homme L, De Roover A, Kohnen L, Scheen AJ, Moutschen M, et al. Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue. Diabetologia. 2013;56:2487–97.

    CAS  PubMed  Article  Google Scholar 

  93. 93.•

    Pereira SS, Teixeira LG, Aguilar EC, Chaves OM, Savassi-Rocha AL, Pelaez JMN, et al. Modulation of Adipose Tissue Inflammation by Foxp3+ Treg Cells, Il-10 and Tgfβ In Metabolically Healthy Class Iii Obese Individuals. Nutrition. 2014. doi:10.1016/j.nut.2013.11.023. This paper studies the visceral and subcutaneous adipose tissue from grade III obese individuals showing that Treg and IL10 are the important to control inflammation in those individuals.

    Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflicts of Interest

Solange S. Pereira and Jacqueline I Alvarez-Leite declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jacqueline I. Alvarez-Leite.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pereira, S.S., Alvarez-Leite, J.I. Low-Grade Inflammation, Obesity, and Diabetes. Curr Obes Rep 3, 422–431 (2014). https://doi.org/10.1007/s13679-014-0124-9

Download citation

Keywords

  • Obesity
  • Inflammation
  • Macrophages
  • Metabolic syndrome
  • Type 2 diabetes mellitus
  • Adipokines