This Article Full Text Full Text (PDF) All Versions of this Article: 148/11/5220    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ropelle, E. R. Articles by Carvalheira, J. B. C. Search for Related Content PubMed PubMed Citation Articles by Ropelle, E. R. Articles by Carvalheira, J. B. C.

A Central Role for Neuronal Adenosine 5'-Monophosphate-Activated Protein Kinase in Cancer-Induced Anorexia

Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas-UNICAMP, 13083-970 Campinas, São Paulo, Brazil

Address all correspondence and requests for reprints to: José B. C. Carvalheira, M.D., Department of Internal Medicine, FCM, State University of Campinas-UNICAMP, 13083-970 Campinas, São Paulo, Brazil. E-mail: carvalheirajbc{at}uol.com.br.

The pathogenesis of cancer anorexia is multifactorial and associated with disturbances of the central physiological mechanisms controlling food intake. However, the neurochemical mechanisms responsible for cancer-induced anorexia are unclear. Here we show that chronic infusion of 5-amino-4imidazolecarboxamide-riboside into the third cerebral ventricle and a chronic peripheral injection of 2 deoxy-D-glucose promotes hypothalamic AMP-activated protein kinase (AMPK) activation, increases food intake, and prolongs the survival of anorexic tumor-bearing (TB) rats. In parallel, the pharmacological activation of hypothalamic AMPK in TB animals markedly reduced the hypothalamic production of inducible nitric oxide synthase, IL-1β, and TNF- and modulated the expression of proopiomelanocortin, a hypothalamic neuropeptide that is involved in the control of energy homeostasis. Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats. Collectively, the findings of this study suggest that hypothalamic AMPK activation reverses cancer anorexia by inhibiting the production of proinflammatory molecules and controlling the neuropeptide expression in the hypothalamus, reflecting in a prolonged life span in TB rats. Thus, our data indicate that hypothalamic AMPK activation presents an attractive opportunity for the treatment of cancer-induced anorexia.

This article has been cited by other articles:

				E. R. Ropelle, J. R. Pauli, M. F. A. Fernandes, S. A. Rocco, R. M. Marin, J. Morari, K. K. Souza, M. M. Dias, M. C. Gomes-Marcondes, J. A.R. Gontijo, et al. A Central Role for Neuronal AMP-Activated Protein Kinase (AMPK) and Mammalian Target of Rapamycin (mTOR) in High-Protein Diet-Induced Weight Loss Diabetes, March 1, 2008; 57(3): 594 - 605. [Abstract] [Full Text] [PDF]