|Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment.|
|PMID: 12376313 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, U.S. Gov't, P.H.S.|
|Title: American journal of physiology. Endocrinology and metabolism Volume: 283 ISSN: 0193-1849 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2002 Nov|
|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|
|Languages: eng Pagination: E867-79 Citation Subset: IM|
|Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|
|APA/MLA Format Download EndNote Download BibTex|
analogs & derivatives*,
Acetyl-CoA Carboxylase / genetics
Amino Acid Sequence
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*
Gene Expression Regulation, Enzymologic / drug effects, physiology
Liver / chemistry
Mice, Inbred BALB C
Molecular Sequence Data
Neurons / chemistry, enzymology*
Neuropeptide Y / analysis, genetics
Obesity / physiopathology
Paraventricular Hypothalamic Nucleus / cytology, physiology*
RNA, Messenger / analysis
|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|
|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 22.214.171.124/malonyl-CoA decarboxylase; EC 6.-/Fatty Acid Synthetase Complex; EC 126.96.36.199/Acetyl-CoA Carboxylase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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