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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-5-31
pubmed:abstractText
Leptin is a hormone that regulates body weight by decreasing food intake and increasing energy expenditure. ob/ob mice carry leptin mutations and are obese and hyperphagic. Leptin administration to lean and ob/ob mice activates a novel metabolic program that depletes adipose tissue. Although this response is physiologically distinct from that evident after food restriction, the molecular nature of these differences is as yet unknown. Expression monitoring of 6500 genes using oligonucleotide microarrays in wild-type, ob/ob, and transgenic mice expressing low levels of leptin revealed that differences in ambient leptin levels have dramatic effects on the phenotype of white 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 was different between leptin treatment and food restriction in ob/ob mice and 10 such clusters in wild-type experiments. One of the clusters was repressed specifically by leptin in both wild-type and ob/ob mice and included several genes known to be regulated by SREBP-1/ADD1. Further studies confirmed that leptin decreases the levels of SREBP-1/ADD1 RNA and transcriptionally active SREBP-1/ADD1 protein in white adipose tissue. Future studies of the molecular basis for the apparent coordinate regulation of the other clusters of leptin-regulated genes may reveal additional mechanisms by which leptin exerts its weight-reducing effects.
pubmed:grant
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0890-9369
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
963-80
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:10783168-Animals, pubmed-meshheading:10783168-Mice, pubmed-meshheading:10783168-Body Weight, pubmed-meshheading:10783168-Female, pubmed-meshheading:10783168-Adipose Tissue, pubmed-meshheading:10783168-Time Factors, pubmed-meshheading:10783168-Cell Differentiation, pubmed-meshheading:10783168-Cluster Analysis, pubmed-meshheading:10783168-Nuclear Proteins, pubmed-meshheading:10783168-Transcription, Genetic, pubmed-meshheading:10783168-Mice, Inbred C57BL, pubmed-meshheading:10783168-Food Deprivation, pubmed-meshheading:10783168-Algorithms, pubmed-meshheading:10783168-Mice, Obese, pubmed-meshheading:10783168-DNA-Binding Proteins, pubmed-meshheading:10783168-Down-Regulation, pubmed-meshheading:10783168-Transcription Factors, pubmed-meshheading:10783168-Gene Expression, pubmed-meshheading:10783168-Blotting, Northern, pubmed-meshheading:10783168-Up-Regulation, pubmed-meshheading:10783168-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:10783168-Mice, Transgenic, pubmed-meshheading:10783168-Sterol Regulatory Element Binding Protein 1
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