Leptin-specific patterns of gene expression in white adipose tissue

Citation
A. Soukas et al., Leptin-specific patterns of gene expression in white adipose tissue, GENE DEV, 14(8), 2000, pp. 963-980
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
GENES & DEVELOPMENT
ISSN journal
0890-9369 → ACNP
Volume
14
Issue
8
Year of publication
2000
Pages
963 - 980
Database
ISI
SICI code
0890-9369(20000415)14:8<963:LPOGEI>2.0.ZU;2-Y
Abstract
Leptin is a hormone that regulates body weight by decreasing food intake an d increasing energy expenditure. ob/ob mice carry leptin mutations and are obese and hyperphagic. Leptin administration to lean and ob/ob mice activat es a novel metabolic program that depletes adipose tissue. Although this re sponse is physiologically distinct from that evident after food restriction , the molecular nature of these differences is as yet unknown. Expression m onitoring of 6500 genes using oligonucleotide microarrays in wild-type, ob/ ob, and transgenic mice expressing low levels of leptin revealed that diffe rences in ambient leptin levels have dramatic effects on the phenotype of w hite adipose tissue. These data identified a large number of genes that are differentially expressed in ob/ob mice. To delineate the components of the transcriptional program specifically affected by leptin, the level of the same 6500 genes was monitored in wild-type and ob/ob mice at various times after leptin treatment or food restriction. A novel application of k-means clustering identified 8 clusters of adipose tissue genes whose expression w as different between leptin treatment and food restriction in ob/ob mice an d 10 such clusters in wild-type experiments. One of the clusters was repres sed specifically by leptin in both wild-type and ob/ob mice and included se veral genes known to be regulated by SREBP-1/ADD1. further studies confirme d that leptin decreases the levels of SREBP-1/ADD1 RNA and transcriptionall y active SREBP-1/ADD1 protein in white adipose tissue. Future studies of th e molecular basis for the apparent coordinate regulation of the other clust ers of leptin-regulated genes may reveal additional mechanisms by which lep tin exerts its weight-reducing effects.