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
© 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 López1, Christopher J. Lelliott1, Sulay Tovar2, Wendy Kimber1, RosalÃ*a Gallego3, Sam Virtue1, Margaret Blount1, Maria J. Vázquez2, Nick Finer1, Trevor J. Powles4, Stephen O’Rahilly1, Asish K. Saha5, Carlos Diéguez2, and Antonio J. Vidal-Puig1
1 Department of Clinical Biochemistry, University of Cambridge, Addenbrooke’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, Addenbrooke’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.
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