PMID- 16644689
OWN - NLM
STAT- MEDLINE
DCOM- 20060626
LR  - 20211020
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 55
IP  - 5
DP  - 2006 May
TI  - Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in 
      the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA.
PG  - 1327-36
AB  - 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.
FAU - Lopez, Miguel
AU  - Lopez M
AD  - Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's 
      Hospital, Hills Road, Cambridge CB2 2QR, U.K.
FAU - Lelliott, Christopher J
AU  - Lelliott CJ
FAU - Tovar, Sulay
AU  - Tovar S
FAU - Kimber, Wendy
AU  - Kimber W
FAU - Gallego, Rosalia
AU  - Gallego R
FAU - Virtue, Sam
AU  - Virtue S
FAU - Blount, Margaret
AU  - Blount M
FAU - Vazquez, Maria J
AU  - Vazquez MJ
FAU - Finer, Nick
AU  - Finer N
FAU - Powles, Trevor J
AU  - Powles TJ
FAU - O'Rahilly, Stephen
AU  - O'Rahilly S
FAU - Saha, Asish K
AU  - Saha AK
FAU - Dieguez, Carlos
AU  - Dieguez C
FAU - Vidal-Puig, Antonio J
AU  - Vidal-Puig AJ
LA  - eng
GR  - G0400192/MRC_/Medical Research Council/United Kingdom
GR  - G9824984/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - DK 19514/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 524-14-1 (Malonyl Coenzyme A)
RN  - 66796-54-1 (Pro-Opiomelanocortin)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
SB  - IM
MH  - Animals
MH  - Anorexia/*chemically induced/enzymology/metabolism
MH  - Body Weight/drug effects
MH  - Energy Intake/drug effects
MH  - Fatty Acid Synthases/*antagonists & inhibitors
MH  - Feeding Behavior/drug effects
MH  - Malonyl Coenzyme A/*metabolism
MH  - Pro-Opiomelanocortin/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tamoxifen/*pharmacology
MH  - Ventromedial Hypothalamic Nucleus/drug effects/*metabolism
MH  - Weight Loss/drug effects
EDAT- 2006/04/29 09:00
MHDA- 2006/06/27 09:00
CRDT- 2006/04/29 09:00
PHST- 2006/04/29 09:00 [pubmed]
PHST- 2006/06/27 09:00 [medline]
PHST- 2006/04/29 09:00 [entrez]
AID - 55/5/1327 [pii]
AID - 10.2337/db05-1356 [doi]
PST - ppublish
SO  - Diabetes. 2006 May;55(5):1327-36. doi: 10.2337/db05-1356.