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The Pathophysiology of Obesity

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Minimally Invasive Bariatric and Metabolic Surgery

Abstract

Obesity has been defined as a “multi-metabolic and hormonal disease state”. Although significant advances have been made in the knowledge of how obesity develops and progresses, our understanding of its etiology and physiopathology is still incomplete.

Calories intake in excess of requirements is stored as fat in the adipose organ. The central nervous system (CNS) and especially the hypothalamus regulates the energy balance receiving afferent signals from the periphery and triggering efferent neuro-hormonal activation aimed at reducing food intake and at increasing energy expenditure. A complex interplay of hormonal substances derived from the gastrointestinal tract with cytokines and other mediators derived from the adipose tissue provide relevant signals to the CNS which regulates satiety and adiposity though secretion of orexigenic or norexigenic peptides.

Multiple etiologic determinants are responsible for obesity development where environmental factors, acting on specific genetic backgrounds, play a prominent role.

On the other hand, the core pathophysiology of obesity consists in the derangement of the central regulation of energy balance with alteration of neuro-chemical and feedback signaling. This in turn produces an inappropriate expansion of the adipose organ with progressive hyper-production of adipokines and especially of inflammatory cytokines. At the systemic level, this translates into atherogenesis and atherosclerosis, hypertension, type 2 diabetes mellitus, increased risk of cardiovascular disease, certain types of tumors and eventually in a reduced life expectancy.

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References

  1. Hoyt l, Burnett L. Should obesity be a disease? N.Y. Times. 2014, Feb. 23, SR 12.

    Google Scholar 

  2. Cinti S. The adipose organ at a glance. Dis Model Mech. 2012;5(5):588–94.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature. 2006;443(7109):289–95.

    Article  CAS  PubMed  Google Scholar 

  4. Lenard NR, Berthoud HR. Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity (Silver Spring). 2008;16 Suppl 3:S11–22.

    Article  CAS  Google Scholar 

  5. Owyang C, Heldsinger A. Vagal control of satiety and hormonal regulation of appetite. J Neurogastroenterol Motil. 2011;17(4):338–48.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Stengel A, Taché Y. Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage. Curr Protein Pept Sci. 2011;12(4):293–304.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Rehfeld JF. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides. Acta Physiol (Oxf). 2011;201(4):405–11.

    Article  CAS  Google Scholar 

  8. Burger KS, Berner LA. A functional neuroimaging review of obesity, appetitive hormones and ingestive behavior. Physiol Behav. 2014;136:121–7.

    Google Scholar 

  9. Mason BL, Wang Q, Zigman JM. The central nervous system sites mediating the orexigenic actions of ghrelin. Annu Rev Physiol. 2014;76:519–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Mietlicki-Baase EG, Hayes MR. Amylin activates distributed CNS nuclei to control energy balance. Physiol Behav. 2014;136:39–46.

    Google Scholar 

  11. Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014;220(2):T47–59.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004;92(3):347–55.

    Article  CAS  PubMed  Google Scholar 

  13. Jéquier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002;967:379–88.

    Article  PubMed  Google Scholar 

  14. Mark AL. Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol. 2013;305(6):R566–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia. 2012;55(9):2319–26.

    Article  CAS  PubMed  Google Scholar 

  16. Lazar MA. Resistin- and obesity-associated metabolic diseases. Horm Metab Res. 2007;39(10):710–6.

    Article  CAS  PubMed  Google Scholar 

  17. Carnell S, Gibson C, Benson L, Ochner CN, Geliebter A. Neuroimaging and obesity: current knowledge and future directions. Obes Rev. 2012;13(1):43–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Del Parigi A, Gautier JF, Chen K, Salbe AD, Ravussin E, Reiman E, Tataranni PA. Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans using positron emission tomography. Ann N Y Acad Sci. 2002;967:389–97.

    Article  PubMed  Google Scholar 

  19. Miras AD, le Roux CW. Mechanisms underlying weight loss after bariatric surgery. Nat Rev Gastroenterol Hepatol. 2013;10(10):575–84.

    Article  PubMed  Google Scholar 

  20. d'Autume C, Musher-Eizenman D, Marinier E, Viarme F, Frelut ML, Isnard P. Eating behaviors and emotional symptoms in childhood obesity: a cross-sectional exploratory study using self-report questionnaires in 63 children and dolescents. Arch Pediatr. 2012;19(8):803–10.

    Article  PubMed  Google Scholar 

  21. O'Rahilly S, Farooqi IS. Human obesity as a heritable disorder of the central control of energy balance. Int J Obes (Lond). 2008;32 Suppl 7:S55–61.

    Article  Google Scholar 

  22. Rhee KE, Phelan S, McCaffery J. Early determinants of obesity: genetic, epigenetic, and in utero influences. Int J Pediatr. 2012;2012:463850.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Drummond EM, Gibney ER. Epigenetic regulation in obesity. Curr Opin Clin Nutr Metab Care. 2013;16(4):392–7.

    CAS  PubMed  Google Scholar 

  24. Mingrone G, Manco M, Mora ME, Guidone C, Iaconelli A, Gniuli D, Leccesi L, Chiellini C, Ghirlanda G. Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care. 2008;31(9):1872–6.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Bray GA. Obesity is a chronic, relapsing neurochemical disease. Int J Obes Relat Metab Disord. 2004;28(1):34–8.

    Article  CAS  PubMed  Google Scholar 

  26. Schäffler A, Müller-Ladner U, Schölmerich J, Büchler C. Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev. 2006;27(5):449–67.

    Article  PubMed  Google Scholar 

  27. Redinger RN. The pathophysiology of obesity and its clinical manifestations. Gastroenterol Hepatol (N Y). 2007;3(11):856–63.

    Google Scholar 

  28. Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 1999;48(6):1270–4.

    Article  CAS  PubMed  Google Scholar 

  29. DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009;32 Suppl 2:S157–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Johnson AM, Olefsky JM. The origins and drivers of insulin resistance. Cell. 2013;152(4):673–84.

    Article  CAS  PubMed  Google Scholar 

  31. Mingrone G, Henriksen FL, Greco AV, Krogh LN, Capristo E, Gastaldelli A, Castagneto M, Ferrannini E, Gasbarrini G, Beck-Nielsen H. Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency. Diabetes. 1999;48(6):1258–63.

    Article  CAS  PubMed  Google Scholar 

  32. Mingrone G, Castagneto M. Role of lipids in insulin resistance and type 2 diabetes mellitus development. Nutrition. 1999;15(1):64–6.

    Article  CAS  PubMed  Google Scholar 

  33. Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, Hoekstra JB, Stroes ES, Nieuwdorp M. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab. 2012;14(2):112–20.

    Article  CAS  PubMed  Google Scholar 

  34. Frezza EE, Shebani KO, Robertson J, Wachtel MS. Morbid obesity causes chronic increase of intraabdominal pressure. Dig Dis Sci. 2007;52(4):1038–41.

    Article  PubMed  Google Scholar 

  35. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.

    Article  PubMed  Google Scholar 

  36. Pischon T, Nöthlings U, Boeing H. Obesity and cancer. Proc Nutr Soc. 2008;67(2):128–45.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Geltrude Mingrone MD, PhD

  2. Department of Surgery, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Marco Castagneto MD

Authors
  1. Geltrude Mingrone MD, PhD
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  2. Marco Castagneto MD
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Corresponding author

Correspondence to Geltrude Mingrone MD, PhD .

Editor information

Editors and Affiliations

  1. General and Emergency Surgery, Bariatric Surgery, Careggi University Hospital, Florence, Italy

    Marcello Lucchese

  2. Department of Surgery, Medical School, University of Genoa, Genoa, Italy

    Nicola Scopinaro

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Mingrone, G., Castagneto, M. (2015). The Pathophysiology of Obesity. In: Lucchese, M., Scopinaro, N. (eds) Minimally Invasive Bariatric and Metabolic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-319-15356-8_3

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  • DOI: https://doi.org/10.1007/978-3-319-15356-8_3

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-15355-1

  • Online ISBN: 978-3-319-15356-8

  • eBook Packages: MedicineMedicine (R0)

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