Document Detail


Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment.
MedLine Citation:
PMID:  12376313     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously demonstrated that C75, a specific and potent inhibitor of fatty acid synthase (FAS), reduced food intake and decreased body weight in mice. In the present study, we determined that these effects were not due to conditioned taste aversion. To investigate the mechanism of C75 action, we examined FAS brain expression. FAS was expressed in a number of brain regions, including arcuate and paraventricular nuclei (PVN) within regions that comprise the arcuate-PVN pathway in mouse and human. Although C75 and fasting significantly downregulated liver FAS, FAS levels remained high in hypothalamus, indicating that FAS levels were regulated differently in brain from those in liver. Double fluorescence in situ for FAS and neuropeptide Y (NPY) showed that FAS co-localized with NPY in neurons in the arcuate nucleus. NPY immnuoreactivity after C75 treatment was decreased in axon terminals that innervate the PVN and lateral hypothalamus. Collectively, these results demonstrate that FAS is present and active in neurons and suggests that C75 may alter food intake via interactions within the arcuate-PVN pathway mediated by NPY.
Authors:
Eun-Kyoung Kim; Ian Miller; Leslie E Landree; Felice F Borisy-Rudin; Pierre Brown; Tarik Tihan; Craig A Townsend; Lee A Witters; Timothy H Moran; Francis P Kuhajda; Gabriele V Ronnett
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  283     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-11     Completed Date:  2002-11-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E867-79     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
4-Butyrolactone / analogs & derivatives*,  pharmacology*
Acetyl-CoA Carboxylase / genetics
Adult
Aged
Amino Acid Sequence
Animals
Appetite / drug effects,  physiology
Arcuate Nucleus / cytology,  physiology*
Carboxy-Lyases / genetics
Conditioning (Psychology) / drug effects,  physiology
Eating / drug effects,  physiology*
Enzyme Inhibitors / pharmacology*
Fasting / physiology
Fatty Acid Synthetase Complex / analysis,  genetics*
Female
Gene Expression Regulation, Enzymologic / drug effects,  physiology
Humans
Immunohistochemistry
Liver / chemistry
Male
Mice
Mice, Inbred BALB C
Middle Aged
Molecular Sequence Data
Neurons / chemistry,  enzymology*
Neuropeptide Y / analysis,  genetics
Obesity / physiopathology
Paraventricular Hypothalamic Nucleus / cytology,  physiology*
RNA, Messenger / analysis
Taste
Grant Support
ID/Acronym/Agency:
CA-87850/CA/NCI NIH HHS; DC-02979/DC/NIDCD NIH HHS; DK-19302/DK/NIDDK NIH HHS; DK-35712/DK/NIDDK NIH HHS; F-32//PHS HHS
Chemical
Reg. No./Substance:
0/4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; 0/Enzyme Inhibitors; 0/Neuropeptide Y; 0/RNA, Messenger; 96-48-0/4-Butyrolactone; EC 4.1.1.-/Carboxy-Lyases; EC 4.1.1.9/malonyl-CoA decarboxylase; EC 6.-/Fatty Acid Synthetase Complex; EC 6.4.1.2/Acetyl-CoA Carboxylase

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