Peptide Antibodies
 
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The recent explosion in obesity research has resurrected many peptides whose functions were either unknown, poorly understood or associated with other bioprocesses not believed to be tied to energy homeostasis. In addition, the reverse pharmacology approach utilizing peptide libraries has been instrumental in identifying new endogenous ligands for the vast array of orphan receptors, many of which have been implicated in obesity. We have attempted to assemble the most up-to-date resource of references, flow charts, obesity peptides and immunology products to assist researchers in their quest to unravel the intricate web of metabolic responses that are responsible for energy homeostasis.








The body produces hormones that act through the brain to regulate short- and long-term appetite and also the body's metabolism. The diagram shows the sources of several of the hormones now under intensive investigation.


The diagram shows the sources of several of the hormones now under intensive investigation.


Marx, J. Cellular Warriors at the Battle of the Bulge.
Feb. 2003. Science: (299): 846-849
Many different hormones control our weight and appetite. The discovery of new peptide hormones, which suppresses appetite for up to 12 hours, may lead to a better understanding of this complex control system.


Hormones that control eating such as, leptin and insulin (lower part of the figure) circulate in the blood at concentrations proportional to body-fat mass. They decrease appetite by inhibiting neurons (centre) that produce the molecules NPY and AGRP, while stimulating melanocortin-producing neurons in the arcuate-nucleus region of the hypothalamus, near the third ventricle of the brain. NPY and AGRP stimulate eating, and melanocortins inhibit eating, via other neurons (top). Activation of NPY/AGRP-expressing neurons inhibits melanocortin-producing neurons. The gastric hormone, ghrelin stimulates appetite by activating the NPY/AGRP-expressing neurons. Batterham and co-workers have shown that PYY (3-36), released from the colon, inhibits these neurons and thereby decreases appetite for up to 12 hours. PYY (3-36) works in part through the auto-inhibitory NPY receptor Y2R.

Michael W. Schwartz and Gregory J. Mortin Nature 418, 595 - 597 (2002)

Central command Centers

The arcuate nucleus (ARC) of the brain contains two sets of neurons with opposing effects. Activation of the AGRP/NPY neurons increases appetite and metabolism, whereas activation of the POMC/CART neurons has the opposite effect. These neurons connect with second-order neurons in other brain centers, and from there the signals are transmitted through the nucleus tratus solitarius (NTS) to the body. Many appetite-regulating hormones work through the ARC, although they may have direct effects on the NTS and other brain centers as well.

Michael W. Schwartz and Gregory J. Mortin Nature 418, 595 - 597 (2002)




References:

  1. Ghrelin induces adiposity in rodents.
    Matthias Tscho� p, David L. Smiley & Mark L. Heiman, Nature, 407, 908-913 (October 19,2000).
  2. Identification of receptors for neuromedin U and its role in feeding.
    Howard A. D., et al., Nature 406 , 70-75 (July 6, 2000)
  3. Alternative role for prolactin-releasing peptide in the regulation of food intake.
    Lawrence CB, et al., Nat Neurosci 2000 Jul;3(7):645-646
  4. Obesity in the new millennium.
    Friedman J. M., Nature 404, 632-634
  5. Centrol Nervous System Control of Food Intake.
    Schwartz M. W. et al. , Nature 404, 661-671
  6. Medical Strategies in the treatment of obesity.
    Bray G. A. and Tartagliat L. A., Nature 404, 672-677
  7. Genetics of body-weight regulation.
    Barsh G. S. et al., Nature 404,644-651
  8. Obesity as a medical Problem.
    Kopelman P. G. Nature 404, 635-643
  9. Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults
    Calle EE, Rodriguez C, Walker-Thurmond, K, and Thun M J. New England J. of Med 2003 Apr: 348 (17): 1625-1638
  10. The emerging science of body weight regulation and its impact on obesity treatment.
    Korner, J. and Aronne LJ. J. Clin. Invest. (2003). 111: 565-570







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