Gene expression profiling identifies liver X receptor alpha as an estrogen-regulated gene in mouse adipose tissue.

• Estrogens reduce adipose tissue mass in both humans and animals. The molecular mechanisms for this effect are, however, not well characterized. We took a gene expression profiling approach to study the direct effects of estrogen on mouse white adipose tissue (WAT). Female ovariectomized mice were treated for 10, 24 and 48 h with 17beta-estradiol or vehicle. RNA was extracted from gonadal fat and hybridized to Affymetrix MG-U74Av2 arrays. 17beta-Estradiol was shown to decrease mRNA expression of liver X receptor (LXR) alpha after 10 h of treatment compared with the vehicle control. The expression of several LXRalpha target genes, such as sterol regulatory element-binding protein 1c, apolipoprotein E, phospholipid transfer protein, ATP-binding cassette A1 and ATP-binding cassette G1, was similarly decreased. We furthermore identified a 1.5 kb LXRalpha promoter fragment that is negatively regulated by estrogen. Several genes involved in lipogenesis and lipolysis were identified as novel targets that could mediate estrogenic effects on adipose tissue. Finally, we show that ERalpha is the main estrogen receptor expressed in mouse white adipose tissue (WAT) with mRNA levels several hundred times higher than those of ERbeta mRNA.

Nyckelord

Adipose Tissue

physiology

Animals

CCAAT-Enhancer-Binding Proteins

genetics

metabolism

Cell Line

Computational Biology

DNA-Binding Proteins

genetics

metabolism

Estrogen Receptor alpha

genetics

metabolism

Estrogen Receptor beta

genetics

metabolism

Estrogens

metabolism

Female

Gene Expression Profiling

Gene Expression Regulation

Genes

Reporter

Humans

Male

Mice

Mice

Inbred C57BL

Molecular Sequence Data

Oligonucleotide Array Sequence Analysis

Ovariectomy

Promoter Regions (Genetics)

Receptors

Cytoplasmic and Nuclear

genetics

metabolism

Sterol Regulatory Element Binding Protein 1

Transcription Factors

genetics

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)