AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 283: E867-E879, 2002. First published July 9, 2002; doi:10.1152/ajpendo.00178.2002
0193-1849/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
283/5/E867    most recent
00178.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (51)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, E.-K.
Right arrow Articles by Ronnett, G. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, E.-K.
Right arrow Articles by Ronnett, G. V.
Vol. 283, Issue 5, E867-E879, November 2002

TRANSLATIONAL PHYSIOLOGY
Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment

Eun-Kyoung Kim1,*, Ian Miller1,*, Leslie E. Landree1, Felice F. Borisy-Rudin1, Pierre Brown1, Tarik Tihan3, Craig A. Townsend6, Lee A. Witters7, Timothy H. Moran5, Francis P. Kuhajda3,4, and Gabriele V. Ronnett1,2

Departments of 1 Neuroscience, 2 Neurology, 3 Pathology, 4 Oncology, and 5 Psychiatry, The Johns Hopkins University School of Medicine, Baltimore 21205; 6 Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218; and 7 Endocrine-Metabolism Division, Departments of Medicine and Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755

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.

appetite; feeding; obesity

* These authors contributed equally to this work.




This article has been cited by other articles:


Home page
 Mol. Interv.Home page
S. R. Bloom, F. P. Kuhajda, I. Laher, X. Pi-Sunyer, G. V. Ronnett, T. M.M. Tan, and D. S. Weigle
The Obesity Epidemic: Pharmacological Challenges
Mol. Interv., April 1, 2008; 8(2): 82 - 98.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. Migrenne, C. Cruciani-Guglielmacci, L. Kang, R. Wang, C. Rouch, A.-L. Lefevre, A. Ktorza, V. H. Routh, B. E. Levin, and C. Magnan
Fatty Acid Signaling in the Hypothalamus and the Neural Control of Insulin Secretion
Diabetes, December 1, 2006; 55(Supplement_2): S139 - S144.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
E. Shumilina, N. Klocker, G. Korniychuk, M. Rapedius, F. Lang, and T. Baukrowitz
Cytoplasmic accumulation of long-chain coenzyme A esters activates KATP and inhibits Kir2.1 channels
J. Physiol., September 1, 2006; 575(2): 433 - 442.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Dridi, C. Ververken, F. B. Hillgartner, A. Lutgarde, E. Van der Gucht, L. Cnops, E. Decuypere, and J. Buyse
FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R138 - R147.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Aja, S. Bi, S. B. Knipp, J. M. McFadden, G. V. Ronnett, F. P. Kuhajda, and T. H. Moran
Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R148 - R154.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Lopez, C. J. Lelliott, S. Tovar, W. Kimber, R. Gallego, S. Virtue, M. Blount, M. J. Vazquez, N. Finer, T. J. Powles, et al.
Tamoxifen-Induced Anorexia Is Associated With Fatty Acid Synthase Inhibition in the Ventromedial Nucleus of the Hypothalamus and Accumulation of Malonyl-CoA.
Diabetes, May 1, 2006; 55(5): 1327 - 1336.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Lu and M. C. Archer
Fatty acid synthase is a potential molecular target for the chemoprevention of breast cancer
Carcinogenesis, January 1, 2005; 26(1): 153 - 157.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. N. Thupari, E.-K. Kim, T. H. Moran, G. V. Ronnett, and F. P. Kuhajda
Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass
Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E97 - E104.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. E. Landree, A. L. Hanlon, D. W. Strong, G. Rumbaugh, I. M. Miller, J. N. Thupari, E. C. Connolly, R. L. Huganir, C. Richardson, L. A. Witters, et al.
C75, a Fatty Acid Synthase Inhibitor, Modulates AMP-activated Protein Kinase to Alter Neuronal Energy Metabolism
J. Biol. Chem., January 30, 2004; 279(5): 3817 - 3827.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online