Advertisement

Models of the Human Metabolism

  • Dirk Langemann
  • Achim Peters
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5232)

Abstract

The systemic investigation of the energy metabolism in the frame of the selfish-brain theory focusses on supply chains. They describe the transport chain beginning with the energy exploration in the remote environment until the energy is consumed by neurons in the brain.

Modeling this, the main difficulty consists in the selection of significant core models among the enormous number of known substances and regulatory mechanisms, which are afflicted with considerable uncertainties in general. We supplement the standard bottom-up modeling of certain mechanisms by a deductive approach. Therefore, we investigate general supply chains and deduce indispensable elements in the regulatory mechanisms from available observations.

A critical selection of system properties and underlying mechanisms enables us to simulate observations, which cannot be explained by the classical glucostatic and lipostatic theory. These observations are the e. g. nearly constant energy level in the brain, the different responses of the periphery and the brain to atrophic periods and finally the development of diabetes.

Keywords

human metabolism supply chains model reduction 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Peters, A., Schweiger, U., Pellerin, L., Hubold, C., Oltmanns, K.M., Conrad, M., Schultes, B., Born, J., Fehm, H.L.: The selfish brain: competition for energy resources. Neurosci. Biobeh. R 28, 143–180 (2004)CrossRefGoogle Scholar
  2. 2.
    Peters, A., Pellerin, L., Dallmann, M.F., Oltmanns, K.M., Schweiger, U., Born, J., Fehm, H.L.: Causes of obesity – looking beyond the hypothalamus. Prog. Neurobiol. 81, 134–143 (2007)CrossRefGoogle Scholar
  3. 3.
    Langemann, D.: Selfish brain theory: mathematical challenges in the top-down analysis of metabolic supply chains. In: Grundy, J. (ed.) ER 2007. LNCS, vol. 4801, pp. 39–49. Springer, Heidelberg (2007)Google Scholar
  4. 4.
    Mayer, J.: Glucostatic mechanism of regulation of food intake. N. Engl. J. Med. 249/1, 13–16 (1953)CrossRefGoogle Scholar
  5. 5.
    Kennedy, G.C.: The role of depot fat in the hypothalamic control of food intake in the rat. Proc. Royal Soc. Lond. B, Biol. Sci. 140/901, 578–592 (1953)CrossRefGoogle Scholar
  6. 6.
    Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., Friedman, J.M.: Positional cloning of the mouse obese gene and its human homologue. Nature 372/6505, 425–432 (1994)CrossRefGoogle Scholar
  7. 7.
    Couzin, J.: Deaths in diabetes trial challenge a long-held theory. Science 319, 884–885 (2008)CrossRefGoogle Scholar
  8. 8.
    Krieger, M.: Über die Atrophie menschlicher Organe bei Inanition [On the human atrophy as a result of undernourishment]. Z. Angew. Anat. Konstitutionsl 7, 87–134 (1921)Google Scholar
  9. 9.
    Oltmanns, K.M., Melchert, U.H., Scholand-Engler, H.G., Howitz, M.C., Schultes, B., Schweiger, U., Hohagen, F., Born, J., Peters, A., Pellerin, L.: Differential energetic response of brain vs.skeletal muscle upon glycemic variations in healthy humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R 12–R 16 (2008)CrossRefGoogle Scholar
  10. 10.
    Magistretti, P.J., Pellerin, L., Rothman, D.L., Shulman, R.G.: Energy on demand. Science 283, 496–497 (1999)CrossRefGoogle Scholar
  11. 11.
    Murray, J.D.: Mathematical Biology. Springer, New York (2002)zbMATHGoogle Scholar
  12. 12.
    Duarte, N.C., Becker, S.A., Jamshidi, N., Thiele, I., Mo, L.M., Vo, T.D., Srivas, R., Palsson, B.Ø.: Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc. Natl. Acad. Sci. 104, 1777–1782 (2007)CrossRefGoogle Scholar
  13. 13.
    Langemann, D., Pellerin, L., Peters, A.: Making sense of AMPA receptor trafficking by modeling molecular mechanisms of synaptic plasticity. Brain Research 1207, 60–72 (2008)CrossRefGoogle Scholar
  14. 14.
    Langemann, D., Peters, A.: Deductive functional assignment of elements in the appetite regulation. J. Biol. Phys. (in print, 2008)Google Scholar
  15. 15.
    Berthoud, H.R.: Mind versus metabolism in the control of food intake and energy balance. Physiol. Behav. 81, 781–793 (2004)CrossRefGoogle Scholar
  16. 16.
    Morton, G.J., Cummings, D.E., Baskin, D.G., Barsh, G.S., Schwartz, M.W.: Central nervous system control of food intake and body weight. Nature 443, 289–295 (2006)CrossRefGoogle Scholar
  17. 17.
    Neary, N.M., Goldstone, A.P., Bloom, S.R.: Appetite regulation: from the gut to the hypothalamus. Clin. Endocrino. 60, 153–160 (2004)CrossRefGoogle Scholar
  18. 18.
    Dallman, M.F., Pecoraro, N., Akana, S.F., la Fleur, S.E., Gomez, F., Houshyar, H., Bell, M.E., Bhatnagar, S., Laugero, K.D., Manalo, S.: Chronic stress and obesity: a new view of comfort food. Proc. Natl. Acad. Sci. 100/20, 11696–11701 (2003)CrossRefGoogle Scholar
  19. 19.
    Petrovich, G.D., Setlow, B., Holland, P.C., Gallagher, M.: Amygdalo-hypothalamic circuit allows learned cues to override satiety and promote eating. J. Neurosci. 22, 8748–8753 (2002)Google Scholar
  20. 20.
    Malik, V.S., Schulze, M.B., Hu, F.B.: Intake of sugar-sweetened beverages and weight gain. Am. J. Clin. Nutr. 84, 274–288 (2006)Google Scholar
  21. 21.
    DiMeglio, D.P., Mattes, R.D.: Liquid versus solid carbohydrate: effects on the food intake and body weight. Int. J. Obesity 24/6, 794–800 (2004)Google Scholar
  22. 22.
    Vannucci, S.J., Maher, F., Simpson, I.A.: Glucose transporter proteins in brain: Delivery of glucose neurons and glia. Glia 21, 2–21 (1997)CrossRefGoogle Scholar
  23. 23.
    Bouret, S.G., Draper, S.J., Simerly, R.B.: Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 108–110 (2004)CrossRefGoogle Scholar
  24. 24.
    Beverly, J.L., de Vries, M.G., Beverly, M.F., Arseneau, L.M.: Norepinephrine mediates glucoprivic-induced increase in GABA in the ventromedial hypothalamus of rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R 990-R 996 (2000)Google Scholar
  25. 25.
    Hubbard, J.H., West, B.H.: Differential Equations: A Dynamical Systems Approach: Higher-Dimensional Systems. Springer, New York (1995)CrossRefzbMATHGoogle Scholar
  26. 26.
    Bingham, N.C., Anderson, K.K., Reuter, A.L., Stallings, N.R., Parker, K.L.: Selective loss of leptin receptors in the ventromedial hypothalamic nucleus results in increase adiposity and a metabolic syndrome. Endocrinology 149(5), 2138–2148 (2008)CrossRefGoogle Scholar
  27. 27.
    Peters, A., Conrad, M., Hubold, C., Schweiger, U., Fischer, B., Fehm, H.L.: The principle of homeostasis in the hypothalamus-pituitary-adrenal system: New insight from positive feedback. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293/1, R 83-R 89 (2007)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Dirk Langemann
    • 1
  • Achim Peters
    • 2
  1. 1.Institute of MathematicsUniversity of LübeckLübeckGermany
  2. 2.Medical Clinic IUniversity of LübeckLübeckGermany

Personalised recommendations