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R.B. · 05-29-2006, 09:42 AM

Tamoxifen mechanisms include acting on the fatty acid synethase pathways.

Women on Tamoxifen may loose weight.

Wider interlinking net works fats diets hormones etc.

"suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior."

RB

Diabetes 55:1327-1336, 2006
DOI: 10.2337/db05-1356
Â© 2006 by the American Diabetes Association
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Tamoxifen-Induced Anorexia Is Associated With Fatty Acid Synthase Inhibition in the Ventromedial Nucleus of the Hypothalamus and Accumulation of Malonyl-CoA

Miguel LÃ³pez1, Christopher J. Lelliott1, Sulay Tovar2, Wendy Kimber1, RosalÃ*a Gallego3, Sam Virtue1, Margaret Blount1, Maria J. VÃ¡zquez2, Nick Finer1, Trevor J. Powles4, Stephen Oâ€™Rahilly1, Asish K. Saha5, Carlos DiÃ©guez2, and Antonio J. Vidal-Puig1

1 Department of Clinical Biochemistry, University of Cambridge, Addenbrookeâ€™s Hospital, Cambridge, U.K
2 Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
3 Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
4 Parkside Oncology Clinic, London, U.K
5 Diabetes Research Unit, EBRC-827, Boston Medical Centre, Boston, Massachusetts

Address correspondence and reprint requests to Antonio J. Vidal-Puig, PhD, MD, Department of Clinical Biochemistry, University of Cambridge, Addenbrookeâ€™s Hospital, Hills Road Cambridge, CB2 2QR, U.K. E-mail: ajv22@cam.ac.uk

ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; ARC, arcuate nucleus of the hypothalamus; CART, cocaine- and amphetamine-regulated transcript; FAS, fatty acid synthase; LHA, lateral hypothalamic area; POMC, proopiomelanocortin; PVN, paraventricular nucleus of the hypothalamus; RMH, Royal Marsden Hospital; TMX, tamoxifen; TOFA, 5-(tetradecyloxy)-2-furoic acid; VMN, ventromedial nucleus of the hypothalamus

Fatty acid metabolism in the hypothalamus has recently been shown to regulate feeding. The selective estrogen receptor modulator tamoxifen (TMX) exerts a potent anorectic effect. Here, we show that the anorectic effect of TMX is associated with the accumulation of malonyl-CoA in the hypothalamus and inhibition of fatty acid synthase (FAS) expression specifically in the ventromedial nucleus of the hypothalamus (VMN). Furthermore, we demonstrate that FAS mRNA expression is physiologically regulated by fasting and refeeding in the VMN but not in other hypothalamic nuclei. Thus, the VMN appears to be the hypothalamic site where regulation of FAS and feeding converge. Supporting the potential clinical relevance of these observations, reanalysis of a primary breast cancer prevention study showed that obese women treated with TMX gained significantly less body weight over a 6-year period than obese women given placebo. The finding that TMX can modulate appetite through alterations in FAS expression and malonyl-CoA levels suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior.

05-29-2006, 09:42 AM	#1
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, .. Tamoxifen mechanisms include acting on the fatty acid synethase pathways. Women on Tamoxifen may loose weight. Wider interlinking net works fats diets hormones etc. "suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior." RB Diabetes 55:1327-1336, 2006 DOI: 10.2337/db05-1356 Â© 2006 by the American Diabetes Association This Article Right arrow Full Text Right arrow Full Text (PDF) Right arrow Online-Only Appendix Right arrow Alert me when this article is cited Right arrow Alert me if a correction is posted Services Right arrow Email this article to a friend Right arrow Similar articles in this journal Right arrow Similar articles in PubMed Right arrow Alert me to new issues of the journal Right arrow Download to citation manager Right arrow Request Permissions Google Scholar Right arrow Articles by LÃ³pez, M. Right arrow Articles by Vidal-Puig, A. J. PubMed Right arrow PubMed Citation Right arrow Articles by LÃ³pez, M. Right arrow Articles by Vidal-Puig, A. J. Tamoxifen-Induced Anorexia Is Associated With Fatty Acid Synthase Inhibition in the Ventromedial Nucleus of the Hypothalamus and Accumulation of Malonyl-CoA Miguel LÃ³pez1, Christopher J. Lelliott1, Sulay Tovar2, Wendy Kimber1, RosalÃ*a Gallego3, Sam Virtue1, Margaret Blount1, Maria J. VÃ¡zquez2, Nick Finer1, Trevor J. Powles4, Stephen Oâ€™Rahilly1, Asish K. Saha5, Carlos DiÃ©guez2, and Antonio J. Vidal-Puig1 1 Department of Clinical Biochemistry, University of Cambridge, Addenbrookeâ€™s Hospital, Cambridge, U.K 2 Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain 3 Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain 4 Parkside Oncology Clinic, London, U.K 5 Diabetes Research Unit, EBRC-827, Boston Medical Centre, Boston, Massachusetts Address correspondence and reprint requests to Antonio J. Vidal-Puig, PhD, MD, Department of Clinical Biochemistry, University of Cambridge, Addenbrookeâ€™s Hospital, Hills Road Cambridge, CB2 2QR, U.K. E-mail: ajv22@cam.ac.uk ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; ARC, arcuate nucleus of the hypothalamus; CART, cocaine- and amphetamine-regulated transcript; FAS, fatty acid synthase; LHA, lateral hypothalamic area; POMC, proopiomelanocortin; PVN, paraventricular nucleus of the hypothalamus; RMH, Royal Marsden Hospital; TMX, tamoxifen; TOFA, 5-(tetradecyloxy)-2-furoic acid; VMN, ventromedial nucleus of the hypothalamus Fatty acid metabolism in the hypothalamus has recently been shown to regulate feeding. The selective estrogen receptor modulator tamoxifen (TMX) exerts a potent anorectic effect. Here, we show that the anorectic effect of TMX is associated with the accumulation of malonyl-CoA in the hypothalamus and inhibition of fatty acid synthase (FAS) expression specifically in the ventromedial nucleus of the hypothalamus (VMN). Furthermore, we demonstrate that FAS mRNA expression is physiologically regulated by fasting and refeeding in the VMN but not in other hypothalamic nuclei. Thus, the VMN appears to be the hypothalamic site where regulation of FAS and feeding converge. Supporting the potential clinical relevance of these observations, reanalysis of a primary breast cancer prevention study showed that obese women treated with TMX gained significantly less body weight over a 6-year period than obese women given placebo. The finding that TMX can modulate appetite through alterations in FAS expression and malonyl-CoA levels suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior.