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Biotech / Medical : Neurocrine Biosciences (NBIX) -- Ignore unavailable to you. Want to Upgrade?

To: Madharry who wrote (1218)	3/18/2004 10:28:26 AM
From: Biomaven	Read Replies (1) \| Respond to of 1834

Nature AOP, published online 17 March 2004; doi:10.1038/nature02440 AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus YASUHIKO MINOKOSHI1, THIERRY ALQUIER1, NOBORU FURUKAWA1, YOUNG-BUM KIM1, ANNA LEE1, BINGZHONG XUE1, JAMES MU2, FABIENNE FOUFELLE3, PASCAL FERRÉ3, MORRIS J. BIRNBAUM2, BETTINA J. STUCK1 & BARBARA B. KAHN1 1 Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA 2 Howard Hughes Medical Institute, The Cox Institute, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA 3 Unit 465 INSERM, Centre de Recherches Biomedicales des Cordeliers, 75270 Paris Cedex 6, France Correspondence and requests for materials should be addressed to B.B.K. (bkahn@bidmc.harvard.edu). Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status1. We investigated the potential role of AMPK in the hypothalamus in the regulation of food intake. Here we report that AMPK activity is inhibited in arcuate and paraventricular hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding. A melanocortin receptor agonist, a potent anorexigen2, decreases AMPK activity in PVH, whereas agouti-related protein, an orexigen2, increases AMPK activity. Melanocortin receptor signalling is required for leptin and refeeding effects on AMPK in PVH. Dominant negative AMPK expression in the hypothalamus is sufficient to reduce food intake and body weight, whereas constitutively active AMPK increases both. Alterations of hypothalamic AMPK activity augment changes in arcuate neuropeptide expression induced by fasting and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects. Thus, hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance. And from the full text: The effect of anorexigenic signals on AMPK activity in PVH appears to be mediated through MC4 [melanocortin 4] receptors Peter