Methods and compositions for modulating leptin activity

A - Human Necessities – 61 – K

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A61K 38/17 (2006.01) A61K 31/00 (2006.01) A61K 31/70 (2006.01) A61K 39/395 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01) C12N 5/10 (2006.01) C12Q 1/68 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2320226

Administration of leptin affects food intake and body weight in animals and humans by a mechanism involving actions on specific regions of the hypothalamus. CIS-1, SOCS-1, SOCS-2 and SOCS-3 genes were investigated for their ability to antagonize leptin action. In mammalian cell lines, SOCS-3 completely blocked leptin induced signal-transduction, whereas CIS, SOCS-1 and SOC-2 were without effect. SOCS-3 is a major target of leptin action in leptin responsive cells in the hypothalamus, and SOCS-3 is a potent inhibitor of leptin signaling. Increased SOCS-3 activity in leptin-responsive neurons is a potential mechanism for the leptin resistance observed in syndromes of obesity, affective mood disorders and reproductive disorders.

L'administration de leptine agit sur l'apport alimentaire et le poids corporel chez les humains et les animaux grâce à un mécanisme qui agit sur des zones spécifiques de l'hypothalamus. On a découvert que les gènes CIS-1, SOCS-1, SOCS-2, ET SOCS-3 produisent des effets antagonistes puissants sur l'action de la leptine. Dans des lignées cellulaires mammifères, le SOCS-3 bloque complètement la transduction de signal induite par la leptine, alors que les CIS, SOCS-1, et SOCS-2 restent sans effet. Le SOCS-3 constitue une cible importante de l'action de la leptine dans les cellules de l'hypothalamus sensibles à la leptine, ainsi qu'un inhibiteur puissant de la signalisation de la leptine. La hausse de l'activité du SOCS-3 dans des neurones sensibles à la leptine constitue un mécanisme potentiel de résistance à la leptine, observée dans les syndromes de l'obésité, les troubles de l'humeur, et les dysfonctionnements des fonctions reproductrices.

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