International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 117 - PROFILING A SMALL MOLECULE-INDUCED LEPTIN-RESISTANCE PHENOTYPE WITH GENE EXPRESSION ANALYSIS OF WHITE ADIPOSE TISSUE

Dr. Takashi Owa
Lab of Seeds Finding Technology, Eisai Co. Ltd
5-1-3 Tokodai
Tsukuba, Ibaraki
300-2635
Japan

Co-Authors: Miyamoto N, Hida T, Nagasu T
Institutions: Lab of Seeds Finding Technology, Eisai Co., Ltd.

The ob gene product leptin regulates body weight by decreasing food intake and increasing energy expenditure. We discovered a compound ER-33672 that caused hyperphagia, marked obesity, and hyperleptinemia to several mouse strains. The injection of exogenous leptin could not overcome the drug effects, suggesting the development of resistance to leptin*s actions. To profile the drug-induced leptin-resistance, array-based gene expression analysis of white adipose tissue was performed with BDF1 mice (7 weeks old, female). When ER-33672 was administered daily for 15 days (day 1-15), mRNAs for a variety of markers generally expressed on macrophages or inflammatory cells were repressed significantly as compared to non-treated control mice. Once drug administration was discontinued on day 15, significant reductions in food intake and body weight were observed, probably due to restored anorexigenic effects of leptin. On day 18, three days after the final drug administration, characteristic down-regulation was observed in a subset of genes involved in fatty acid or cholesterol biosynthesis. The induction of various inflammatory genes was also prominent on the same day. Hyperleptinemia and coincidental leptin-resistance appears to accompany human obesity. Therefore, the chemical approach shown here may provide useful information for functional genomic studies of leptin signaling and obesity-related abnormalities.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012