Genomics Inform.  2008 Sep;6(3):117-125.

Gene Expression Profiling in C57BL/6 Mice Treated with the Anorectic Drugs Sibutramine and Phendimetrazine and Their Mechanistic Implications

• Ko MJ
• Choi HS
• Ahn JI
• Kim SY
• Jeong HS
• Chung HJ

Abstract

Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.

Keyword

microarray; gene expression; anorectic drug; sibutramine; phendimetrazine; methamphetamine

MeSH Terms

Animals
Appetite
Appetite Depressants
Body Weight Changes
Cyclobutanes
Drug Tolerance
Gene Expression
Gene Expression Profiling
Hypothalamus
Methamphetamine
Mice
Morpholines
Obesity
Public Health
Smell
Transcriptome
Up-Regulation
Appetite Depressants
Cyclobutanes
Methamphetamine
Morpholines