Regulation of human adipocyte gene expression by thyroid hormone.
Thyroid hormones are key regulators of metabolism. In adipose tissue, changes in thyroid status result in alterations of lipolytic capacity. The effects of these hormones are mediated by thyroid hormone receptors that modulate gene transcription. Very few target genes have been identified in adipose tissue. To investigate the effect of T(3) on gene expression in human adipocytes, primary cultures of human sc adipose tissue explants were treated with T(3). (32)P-labeled cDNA probes prepared from isolated adipocyte total RNA were hybridized to cDNA arrays representing 1,176 genes. Among the statistically significant variations in mRNA levels with more than 1.3-fold difference, 13 and 6 genes were positively and negatively regulated, respectively (n = 3). The genes encoded proteins that were involved in signal transduction, lipid metabolism, apoptosis, and inflammatory response. Using RT-competitive PCR, we showed a down-regulation of phosphodiesterase 3B, alpha(2A)-adrenergic receptor, and G protein alpha(i2) subunit mRNAs, and an up-regulation of beta(2)-adrenergic receptor mRNA. These regulations may explain the T(3)-mediated increase in catecholamine-induced lipolysis. The down-regulation of sterol regulatory element binding protein-1c, a transcription factor controlling lipogenic gene expression, may constitute a link between thyrotoxicosis and insulin resistance. Thus, these data suggest that T(3) modulates expression of genes with a wide range of function in human adipose tissue.
Viguerie
Nathalie
N
INSERM Unit 317, Institut Louis Bugnard, Université Paul Sabatier, Hôpital Rangueil, 31403 Toulouse Cedex 4, France. viguenat@rangueil.inserm.fr
Millet
Laurence
L
Avizou
Sebastien
S
Vidal
Hubert
H
Larrouy
Dominique
D
Langin
Dominique
D
D017667:Adipocytes / Q000502:physiology*; D000328:Adult; D046508:Culture Techniques; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014284:Triiodothyronine / Q000494:pharmacology*; D015854:Up-Regulation
D007527:Isoenzymes; D020033:Protein Isoforms; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D010727:Phosphoric Diester Hydrolases; D020962:Heterotrimeric GTP-Binding Proteins