Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Reviews

Bariatric surgery, adipose tissue and gut microbiota

International Journal of Obesity volume 35, pages S7–S15 (2011)Cite this article

Subjects

Abstract

Human obesity can be viewed as a set of phenotypes that evolve over time in a sequence of stages that need to be precisely measured. Environmental, behavioral, genetic and biological factors interact to cause obesity. This presentation provides a clinical viewpoint on some biological processes that may explain some of the stages in the development of human obesity, its chronic maintenance and occurrence of complications, with a focus on brain structures, genetics, the profound alterations in adipose tissue biology and gut microbiota components. Roux-en-Y gastric bypass surgery is an increasingly effective model to study in this context because it leads to major improvements in glucose and lipid homeostasis and to the amelioration of some systemic inflammatory markers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM et al. Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond) 2006; 30: 1585–1594.

    Article  CAS  Google Scholar 

  2. Hawley JA, Holloszy JO . Exercise: it's the real thing! Nutr Rev 2009; 67: 172–178.

    Article  Google Scholar 

  3. Patel SR, Hu FB . Short sleep duration and weight gain: a systematic review. Obesity (Silver Spring) 2008; 16: 643–653.

    Article  Google Scholar 

  4. Hill JO, Wyatt HR, Reed GW, Peters JC . Obesity and the environment: where do we go from here? Science 2003; 299: 853–855.

    Article  CAS  Google Scholar 

  5. Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 2007; 13: 803–811.

    Article  CAS  Google Scholar 

  6. Casals-Casas C, Feige JN, Desvergne B . Interference of pollutants with PPARs: endocrine disruption meets metabolism. Int J Obes (Lond) 2008; 32 (Suppl 6): S53–S61.

    Article  CAS  Google Scholar 

  7. Kim MJ, Marchand P, Henegar C, Antignac JP, Alili R, Poitou C et al. Fate and complex pathogenic effects of dioxins and polychlorinated biphenyls in obese subjects before and after drastic weight loss. Environ Health Perspect 2011; 119: 377–383.

    Article  CAS  Google Scholar 

  8. Round JL, Mazmanian SK . The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009; 9: 313–323.

    Article  CAS  Google Scholar 

  9. van Ginneken V, Sitnyakowsky L, Jeffery JE . Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity. Med Hypotheses 2009; 72: 383–388.

    Article  Google Scholar 

  10. Clément K, Sørensen TIA (eds). Obesity: Genomics and Postgenomics. Informa Healthcare, 2007, pp 1–600 (ISBN 978-0-8493-8089-1).

    Book  Google Scholar 

  11. Prentice AM, Hennig BJ, Fulford AJ . Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? Int J Obes (Lond) 2008; 32: 1607–1610.

    Article  CAS  Google Scholar 

  12. Sorensen TI . Conference on ‘multidisciplinary approaches to nutritional problems’. Symposium on ‘diabetes and health’. Challenges in the study of causation of obesity. Proc Nutr Soc 2009; 68: 43–54.

    Article  Google Scholar 

  13. Savage DB, Petersen KF, Shulman GI . Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 2007; 87: 507–520.

    Article  CAS  Google Scholar 

  14. Coll AP, Yeo GS, Farooqi IS, O’Rahilly S . SnapShot: the hormonal control of food intake. Cell 2008; 135: 572; e1–2.

    Article  CAS  Google Scholar 

  15. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW . Central nervous system control of food intake and body weight. Nature 2006; 443: 289–295.

    Article  CAS  Google Scholar 

  16. Nahon JL . The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis. C R Biol 2006; 329: 623–638; discussion 653–655.

    Article  CAS  Google Scholar 

  17. Coppari R, Ramadori G, Elmquist JK . The role of transcriptional regulators in central control of appetite and body weight. Nat Clin Pract Endocrinol Metab 2009; 5: 160–166.

    CAS  PubMed  Google Scholar 

  18. Scarpace PJ, Zhang Y . Leptin resistance: a prediposing factor for diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 2009; 296: R493–R500.

    Article  CAS  Google Scholar 

  19. Migrenne S, Marsollier N, Cruciani-Guglielmacci C, Magnan C . Importance of the gut-brain axis in the control of glucose homeostasis. Curr Opin Pharmacol 2006; 6: 592–597.

    Article  CAS  Google Scholar 

  20. Guyon A, Massa F, Rovere C, Nahon JL . How cytokines can influence the brain: a role for chemokines? J Neuroimmunol 2008; 198: 46–55.

    Article  CAS  Google Scholar 

  21. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 2007; 449: 228–232.

    Article  CAS  Google Scholar 

  22. Bouchard C . Gene-environment interactions in the etiology of obesity: defining the fundamentals. Obesity (Silver Spring) 2008; 16 (Suppl 3): S5–S10.

    Article  CAS  Google Scholar 

  23. Mutch DM, Clement K . Unraveling the genetics of human obesity. PLoS Genet 2006; 2: e188.

    Article  Google Scholar 

  24. Junien C, Nathanielsz P . Report on the IASO Stock Conference 2006: early and lifelong environmental epigenomic programming of metabolic syndrome, obesity and type II diabetes. Obes Rev 2007; 8: 487–502.

    Article  CAS  Google Scholar 

  25. Chung WK, Leibel RL . Molecular physiology of syndromic obesities in humans. Trends Endocrinol Metab 2005; 16: 267–272.

    Article  CAS  Google Scholar 

  26. Farooqi IS, O’Rahilly S . Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 2008; 4: 569–577.

    Article  CAS  Google Scholar 

  27. Hardy J, Singleton A . Genomewide association studies and human disease. N Engl J Med 2009; 360: 1759–1768.

    Article  CAS  Google Scholar 

  28. Leibel RL . Energy in, energy out, and the effects of obesity-related genes. N Engl J Med 2008; 359: 2603–2604.

    Article  CAS  Google Scholar 

  29. Hofker M, Wijmenga C . A supersized list of obesity genes. Nat Genet 2009; 41: 139–140.

    Article  CAS  Google Scholar 

  30. Qi L, Cho YA . Gene-environment interaction and obesity. Nutr Rev 2008; 66: 684–694.

    Article  Google Scholar 

  31. Cinti S . The adipose organ. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 9–15.

    Article  CAS  Google Scholar 

  32. Arner P, Langin D . The role of neutral lipases in human adipose tissue lipolysis. Curr Opin Lipidol 2007; 18: 246–250.

    Article  CAS  Google Scholar 

  33. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114: 1752–1761.

    Article  CAS  Google Scholar 

  34. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004; 306: 457–461.

    Article  Google Scholar 

  35. Boden G, Duan X, Homko C, Molina EJ, Song W, Perez O et al. Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 2008; 57: 2438–2444.

    Article  CAS  Google Scholar 

  36. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007; 56: 901–911.

    Article  CAS  Google Scholar 

  37. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796–1808.

    Article  CAS  Google Scholar 

  38. Sethi JK, Vidal-Puig AJ . Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 2007; 48: 1253–1262.

    Article  CAS  Google Scholar 

  39. Ailhaud G . Adipose tissue as a secretory organ: from adipogenesis to the metabolic syndrome. C R Biol 2006; 329: 570–577; discussion 653–655.

    Article  CAS  Google Scholar 

  40. Rosen ED, MacDougald OA . Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 2006; 7: 885–896.

    Article  CAS  Google Scholar 

  41. Rosen ED, Spiegelman BM . Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444: 847–853.

    Article  CAS  Google Scholar 

  42. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O et al. Dynamics of fat cell turnover in humans. Nature 2008; 453: 783–787.

    Article  CAS  Google Scholar 

  43. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA . The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 2001; 280: E827–E847.

    Article  CAS  Google Scholar 

  44. Guerre-Millo M . Adipose tissue and adipokines: for better or worse. Diabetes Metab 2004; 30: 13–19.

    Article  CAS  Google Scholar 

  45. Skurk T, Alberti-Huber C, Herder C, Hauner H . Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92: 1023–1033.

    Article  CAS  Google Scholar 

  46. Nijhuis J, Rensen SS, Slaats Y, van Dielen FM, Buurman WA, Greve JW . Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity (Silver Spring) 2009; 17: 2014–2018.

    Article  CAS  Google Scholar 

  47. 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: 914–920.

    Article  CAS  Google Scholar 

  48. Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I, Guerre-Millo M et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol 2008; 9: R14.

    Article  Google Scholar 

  49. Curat CA, Miranville A, Sengenes C, Diehl M, Tonus C, Busse R et al. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 2004; 53: 1285–1292.

    Article  CAS  Google Scholar 

  50. Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 2006; 55: 1554–1561.

    Article  CAS  Google Scholar 

  51. Caspar-Bauguil S, Cousin B, Andre M, Nibbelink M, Galinier A, Periquet B et al. Weight-dependent changes of immune system in adipose tissue: importance of leptin. Exp Cell Res 2006; 312: 2195–2202.

    Article  CAS  Google Scholar 

  52. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 2008; 28: 1304–1310.

    Article  CAS  Google Scholar 

  53. Liu J, Divoux A, Sun J, Zhang J, Clement 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: 940–945.

    Article  CAS  Google Scholar 

  54. Villaret A, Galitzky J, Decaunes P, Esteve D, Marques MA, Sengenes C et al. Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. Diabetes 2010; 59: 2755–2763.

    Article  CAS  Google Scholar 

  55. Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K . Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 2007; 148: 868–877.

    Article  CAS  Google Scholar 

  56. Keophiphath M, Achard V, Henegar C, Rouault C, Clement K, Lacasa D . Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol 2009; 23: 11–24.

    Article  CAS  Google Scholar 

  57. Constant VA, Gagnon A, Landry A, Sorisky A . Macrophage-conditioned medium inhibits the differentiation of 3T3-L1 and human abdominal preadipocytes. Diabetologia 2006; 49: 1402–1411.

    Article  CAS  Google Scholar 

  58. 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: 2347–2355.

    Article  CAS  Google Scholar 

  59. 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 alpha. Arterioscler Thromb Vasc Biol 2005; 25: 2062–2068.

    Article  CAS  Google Scholar 

  60. Permana PA, Menge C, Reaven PD . Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun 2006; 341: 507–514.

    Article  CAS  Google Scholar 

  61. Chun TH, Hotary KB, Sabeh F, Saltiel AR, Allen ED, Weiss SJ . A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell 2006; 125: 577–591.

    Article  CAS  Google Scholar 

  62. Pasarica M, Gowronska-Kozak B, Burk D, Remedios I, Hymel D, Gimble J et al. Adipose tissue collagen VI in obesity. J Clin Endocrinol Metab 2009; 94: 5155–5162.

    Article  CAS  Google Scholar 

  63. Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 2010; 59: 2817–2825.

    Article  CAS  Google Scholar 

  64. Tordjman J, Poitou C, Hugol D, Bouillot JL, Basdevant A, Bedossa P et al. Association between omental adipose tissue macrophages and liver histopathology in morbid obesity: influence of glycemic status. J Hepatol 2009; 51: 354–362.

    Article  CAS  Google Scholar 

  65. van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 2008; 48: 449–457.

    Article  Google Scholar 

  66. Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357: 741–752.

    Article  Google Scholar 

  67. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277–2286.

    Article  CAS  Google Scholar 

  68. Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A et al. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 2009; 94: 4619–4623.

    Article  CAS  Google Scholar 

  69. Capel F, Klimcakova E, Viguerie N, Roussel B, Vitkova M, Kovacikova M et al. Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization. Diabetes 2009; 58: 1558–1567.

    Article  CAS  Google Scholar 

  70. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA 2009; 106: 2365–2370.

    Article  CAS  Google Scholar 

  71. 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: 3049–3057.

    Article  CAS  Google Scholar 

  72. Cani PD, Delzenne NM . Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharmacol 2009; 9: 737–743.

    Article  CAS  Google Scholar 

  73. Zeyda M, Farmer D, Todoric J, Aszmann O, Speiser M, Gyori G et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond) 2007; 31: 1420–1428.

    Article  CAS  Google Scholar 

  74. Lumeng CN, Bodzin JL, Saltiel AR . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175–184.

    Article  CAS  Google Scholar 

  75. Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR . Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 2007; 56: 16–23.

    Article  CAS  Google Scholar 

  76. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS . TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006; 116: 3015–3025.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank Dr Joan Tordjman for her contribution to the iconography.

Author information

Authors and Affiliations

  1. Cardiometabolism Division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France

    K Clément

  2. INSERM, U872, Nutriomique, Paris, France

    K Clément

  3. Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, Paris, France

    K Clément

Authors
  1. K Clément
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Clément.

Ethics declarations

Competing interests

Nutriomic projects on inflammation are supported by the Region Ile de France, the Commission of the European Communities (Collaborative Project ADAPT, contract number HEALTH-F2-2008-201100), Hepadip (http://www.hepadip.org/, contract LSHM-CT-2005-018734 and FLIP (Seventh Framework Programme (FP7/2007-2013) under grant agreement no. Health-F2-2009-241762).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clément, K. Bariatric surgery, adipose tissue and gut microbiota. Int J Obes 35 (Suppl 3), S7–S15 (2011). https://doi.org/10.1038/ijo.2011.141

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2011.141

Keywords

This article is cited by

Search

Advanced search

Quick links