Effects of estrogen on gene expression profiles in mouse hypothalamus and white adipose tissue: target genes include glutathione peroxidase 3 and cell death-inducing DNA fragmentation factor, alpha-subunit-like effector A.
Obesity has become a major health problem in many parts of the world. Estrogens are known to reduce adipose tissue mass in both humans and animals but the molecular mechanisms are not well characterized. We used gene expression profiling to study long-term effects of estrogen on gene expression in mouse white adipose tissue and hypothalamus. Overall, the effects of estrogen on hypothalamic gene expression were much smaller than the corresponding effects on white adipose tissue gene expression. We characterize in detail estrogenic regulation of glutathione peroxidase 3 (GPX3). Our studies suggest that GPX3 is a direct estrogen receptor alpha target gene in white adipose tissue. Since obesity is correlated with oxidative stress, and GPX3 has been demonstrated to be lower in obesity and higher after weight loss, we hypothesize that GPX3 is one important mediator of effects of estrogen in relation to fat mass. Additional genes that were affected by estrogen in adipose tissue include cell death-inducing DNA fragmentation factor, alpha-subunit-like effector A (CIDEA), a gene shown to be related to body fat in mice. We conclude that estrogen has large effects on gene expression in white adipose tissue and hypothesize that GPX3 and CIDEA could be important mediators of the effects of estrogen on fat mass.
Lundholm
Lovisa
L
Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-141 57 Huddinge, Sweden. lovisa.lundholm@biosci.ki.se
Putnik
Milica
M
Otsuki
Michio
M
Andersson
Sandra
S
Ohlsson
Claes
C
Gustafsson
Jan-Ake
JA
Dahlman-Wright
Karin
K
D052436:Adipose Tissue, White / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D053938:DNA Fragmentation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000235:genetics*; D007031:Hypothalamus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D012333:RNA, Messenger; D004958:Estradiol; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase