Skip to main content
SpringerLink
Log in

Pathophysiology of Obesity

  • Chapter
  • First Online:
Bariatric Endoscopy

  • 1408 Accesses

Abstract

Despite day-to-day variations in caloric intake and expenditure, the regulation of body weight is precisely controlled over long periods of time. To achieve this objective, the body possesses a wide and complex network of neuroendocrine signals originating in the gastrointestinal system, the central nervous system, and adipose tissue, among other sources to regulate both short- and long-term balances between energy intake and energy expenditure. A better understanding of the central and peripheral factors involved, particularly the role of gut hormones, will pave the way for development of improved treatment modalities for obesity.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kennedy GC. The hypothalamic control of food intake in rats. Proc R Soc Lond B Biol Sci. 1950; 137(889):535–49.

    Article  PubMed  CAS  Google Scholar 

  2. Bruce HM, Kennedy GC. The central nervous control of food and water intake. Proc R Soc Lond B Biol Sci. 1951;138(893):528–44.

    Article  PubMed  CAS  Google Scholar 

  3. Mayer J, Barnett RJ. Obesity following unilateral hypothalamic lesions in rats. Science. 1955;121(3147): 599–600.

    Article  PubMed  CAS  Google Scholar 

  4. Morrison SD, Barrnett RJ, Mayer J. Localization of lesions in the lateral hypothalamus of rats with induced adipsia and aphagia. Am J Physiol. 1958; 193(1):230–4.

    PubMed  CAS  Google Scholar 

  5. Coleman DL. Effects of parabiosis of obese with ­diabetes and normal mice. Diabetologia. 1973; 9(4):294–8.

    Article  PubMed  CAS  Google Scholar 

  6. Coleman DL, Hummel KP. Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol. 1969;217(5):1298–304.

    PubMed  CAS  Google Scholar 

  7. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372(6505):425–32. Erratum in: Nature. Mar 30, 1995; 374(6521):479.

    Google Scholar 

  8. Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263–71.

    Article  PubMed  CAS  Google Scholar 

  9. Ahima RS, Antwi DA. Brain regulation of appetite and satiety. Endocrinol Metab Clin North Am. 2008; 37(4):811–23.

    Article  PubMed  CAS  Google Scholar 

  10. Farooqi S, Rau H, Whitehead J, O’Rahilly S. ob gene mutations and human obesity. Proc Nutr Soc. 1998; 57(3):471–5.

    Article  PubMed  CAS  Google Scholar 

  11. Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998;392(6674):398–401.

    Article  PubMed  Google Scholar 

  12. Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543–6.

    Article  PubMed  CAS  Google Scholar 

  13. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879–84.

    Article  PubMed  CAS  Google Scholar 

  14. Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002;110(8):1093–103.

    PubMed  CAS  Google Scholar 

  15. Münzberg H, Myers Jr MG. Molecular and anatomical determinants of central leptin resistance. Nat Neurosci. 2005;8(5):566–70.

    Article  PubMed  Google Scholar 

  16. Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a ­neural network in the arcuate nucleus. Nature. 2001; 411(6836):480–4.

    Article  PubMed  CAS  Google Scholar 

  17. Elias CF, Aschkenasi C, Lee C, et al. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron. 1999;23(4): 775–86.

    Article  PubMed  CAS  Google Scholar 

  18. Cusin I, Zakrzewska KE, Boss O, et al. Chronic ­central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins. Diabetes. 1998;47(7):1014–9.

    Article  PubMed  CAS  Google Scholar 

  19. Unger RH. Lipotoxic diseases. Annu Rev Med. 2002;53:319–36.

    Article  PubMed  CAS  Google Scholar 

  20. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1(1):15–25.

    Article  PubMed  CAS  Google Scholar 

  21. Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes. 2001;50(5):1126–33.

    Article  PubMed  CAS  Google Scholar 

  22. Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8(7):731–7.

    Article  PubMed  CAS  Google Scholar 

  23. Weyer C, Funahashi T, Tanaka S, et al. Hypoadi-ponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930–5.

    Article  PubMed  CAS  Google Scholar 

  24. Abbasi F, Chu JW, Lamendola C, et al. Discrimination between obesity and insulin resistance in the relationship with adiponectin. Diabetes. 2004;53(3):585–90.

    Article  PubMed  CAS  Google Scholar 

  25. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79–83.

    Article  PubMed  CAS  Google Scholar 

  26. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20(6):1595–9.

    Article  PubMed  CAS  Google Scholar 

  27. Monzillo LU, Hamdy O, Horton ES, et al. Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res. 2003;11(9): 1048–54.

    Article  PubMed  CAS  Google Scholar 

  28. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248–56.e5.

    Article  PubMed  Google Scholar 

  29. Butner KL, Nickols-Richardson SM, Clark SF, Ramp WK, Herbert WG. A review of weight loss following Roux-en-Y gastric bypass vs restrictive bariatric surgery: impact on adiponectin and insulin. Obes Surg. 2010;20(5):559–68.

    Article  PubMed  Google Scholar 

  30. Moschen AR, Molnar C, Wolf AM, et al. Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol. 2009;51(4):765–77.

    Article  PubMed  CAS  Google Scholar 

  31. Krakoff J, Funahashi T, Stehouwer CD, et al. Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care. 2003;26(6): 1745–51.

    Article  PubMed  CAS  Google Scholar 

  32. Muse ED, Obici S, Bhanot S, et al. Role of resistin in diet-induced hepatic insulin resistance. J Clin Invest. 2004;114(2):232–9.

    PubMed  CAS  Google Scholar 

  33. Rajala MW, Qi Y, Patel HR, et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004;53(7):1671–9.

    Article  PubMed  CAS  Google Scholar 

  34. Gharibeh MY, Al Tawallbeh GM, Abboud MM, Radaideh A, Alhader AA, Khabour OF. Correlation of plasma resistin with obesity and insulin resistance in type 2 diabetic patients. Diabetes Metab. 2010; 36(6 pt 1):443–9.

    Article  PubMed  CAS  Google Scholar 

  35. Ollmann MM, Wilson BD, Yang YK, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997; 278(5335):135–8. Erratum in: Science. Sep 11, 1998; 281(5383):1615.

    Google Scholar 

  36. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88(1):131–41.

    Article  PubMed  CAS  Google Scholar 

  37. Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest. 2000;106(2):253–62.

    Article  PubMed  CAS  Google Scholar 

  38. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insuffi-ciency and red hair pigmentation caused by POMC ­mutations in humans. Nat Genet. 1998;19(2):155–7.

    Article  PubMed  CAS  Google Scholar 

  39. Krude H, Biebermann H, Gruters A. Mutations in the human proopiomelanocortin gene. Ann N Y Acad Sci. 2003;994:233–9.

    Article  PubMed  CAS  Google Scholar 

  40. Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol. 1973;84(3):488–95.

    Article  PubMed  CAS  Google Scholar 

  41. Reidelberger RD, O’Rourke MF. Potent cholecystokinin antagonist L 364718 stimulates food intake in rats. Am J Physiol. 1989;257(6 Pt 2):R1512–8.

    PubMed  CAS  Google Scholar 

  42. Smith GP, Jerome C, Cushin BJ, Eterno R, Simansky KJ. Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science. 1981;213(4511):1036–7.

    Article  PubMed  CAS  Google Scholar 

  43. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–60.

    Article  PubMed  CAS  Google Scholar 

  44. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407(6806):908–13.

    Article  PubMed  Google Scholar 

  45. Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86(12):5992.

    Article  PubMed  CAS  Google Scholar 

  46. Cummings DE, Shannon MH. Roles for ghrelin in the regulation of appetite and body weight. Arch Surg. 2003;138(4):389–96.

    Article  PubMed  CAS  Google Scholar 

  47. Tritos NA, Mun E, Bertkau A, Grayson R, Maratos-Flier E, Goldfine A. Serum ghrelin levels in response to glucose load in obese subjects post-gastric bypass surgery. Obes Res. 2003;11(8):919–24.

    Article  PubMed  CAS  Google Scholar 

  48. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346(21):1623–30.

    Article  PubMed  Google Scholar 

  49. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003;349(10):941–8.

    Article  PubMed  CAS  Google Scholar 

  50. Witte AB, Grybäck P, Holst JJ, et al. Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man. Regul Pept. 2009;158(1–3):57–62.

    Article  PubMed  CAS  Google Scholar 

  51. Kuenzel WJ, Douglass LW, Davison BA. Robust feeding following central administration of neuropeptide Y or peptide YY in chicks, Gallus domesticus. Peptides. 1987;8(5):823–8.

    Article  PubMed  CAS  Google Scholar 

  52. Alvarez Bartolomé M, Borque M, Martinez-Sarmiento J, et al. Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty. Obes Surg. 2002;12(3):324–7.

    Article  PubMed  Google Scholar 

  53. Jin SL, Han VK, Simmons JG, Towle AC, Lauder JM, Lund PK. Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study. J Comp Neurol. 1988;271(4):519–32.

    Article  PubMed  CAS  Google Scholar 

  54. Moran TH. Gut peptides in the control of food intake. Int J Obes (Lond). 2009;33 Suppl 1:S7–10.

    Article  CAS  Google Scholar 

  55. Drucker DJ. Glucagon-like peptides. Diabetes. 1998;47(2):159–69.

    Article  PubMed  CAS  Google Scholar 

  56. Verdich C, Toubro S, Buemann B, Lysgård Madsen J, Juul Holst J, Astrup A. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction. Int J Obes Relat Metab Disord. 2001;25(8):1206–14.

    Article  PubMed  CAS  Google Scholar 

  57. Näslund E, King N, Mansten S, et al. Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects. Br J Nutr. 2004; 91(3):439–46.

    Article  PubMed  Google Scholar 

  58. Laferrère B, Heshka S, Wang K, Khan Y, McGinty J, Teixeira J, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30(7):1709–16. Epub 2007 Apr 6.

    Article  PubMed  Google Scholar 

  59. Le Quellec A, Kervran A, Blache P, Ciurana AJ, Bataille D. Oxyntomodulin-like immunoreactivity: diurnal profile of a new potential enterogastrone. J Clin Endocrinol Metab. 1992;74(6):1405–9.

    Article  PubMed  Google Scholar 

  60. Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786–95.

    Article  CAS  Google Scholar 

  61. Cohen MA, Ellis SM, Le Roux CW, et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003; 88(10):4696–701.

    Article  PubMed  CAS  Google Scholar 

  62. Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240(2):236–42.

    Article  PubMed  Google Scholar 

  63. Pasarica M, Dhurandhar NV. Infectobesity: obesity of infectious origin. Adv Food Nutr Res. 2007;52:61–102.

    Article  PubMed  CAS  Google Scholar 

  64. Burcelin R, Luche E, Serino M. The gut microbiota ecology: a new opportunity for the treatment of metabolic diseases? Amar J Front Biosci. 2009;14:5107.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Gastrointestinal Metabolic Surgery, Weill Cornell Medical College, Cornell University, New York Presbyterian Hospital, 525 E. 68th Street, New York, NY, 10065, USA

    Alpana P. Shukla M.D., M.R.C.P., Marlus Moreira M.D. & Francesco Rubino M.D.

Authors
  1. Alpana P. Shukla M.D., M.R.C.P.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marlus Moreira M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco Rubino M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesco Rubino M.D. .

Editor information

Editors and Affiliations

  1. Harvard Medical School, Division of Gastroenterology,, Brigham and Women's Hospital, 75 Francis St, ASB2, Boston, 02115, Massachusetts, USA

    Christopher C. Thompson

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Shukla, A.P., Moreira, M., Rubino, F. (2013). Pathophysiology of Obesity. In: Thompson, C. (eds) Bariatric Endoscopy. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1710-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-1710-2_2

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-1709-6

  • Online ISBN: 978-1-4419-1710-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation