Faculty Collaboration Database

Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment. Am J Physiol Endocrinol Metab 2002 Nov;283(5):E867-79

Date

10/12/2002

Pubmed ID

12376313

DOI

10.1152/ajpendo.00178.2002

Scopus ID

2-s2.0-0036841351 (requires institutional sign-in at Scopus site)   123 Citations

Abstract

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.

Author List

Kim EK, Miller I, Landree LE, Borisy-Rudin FF, Brown P, Tihan T, Townsend CA, Witters LA, Moran TH, Kuhajda FP, Ronnett GV

Author

Felice F. Borisy-Rudin JD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

4-Butyrolactone
Acetyl-CoA Carboxylase
Adult
Aged
Amino Acid Sequence
Animals
Appetite
Arcuate Nucleus of Hypothalamus
Carboxy-Lyases
Eating
Enzyme Inhibitors
Fasting
Fatty Acid Synthases
Female
Gene Expression Regulation, Enzymologic
Humans
Immunohistochemistry
Liver
Male
Mice
Mice, Inbred BALB C
Middle Aged
Molecular Sequence Data
Neurons
Neuropeptide Y
Obesity
Paraventricular Hypothalamic Nucleus
RNA, Messenger
Taste