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, α-subunit-like effector A

• Published in: Journal of endocrinology Vol. 196; no. 3; pp. 547 - 557
• Main Authors: Lundholm, Lovisa, Putnik, Milica, Otsuki, Michio, Andersson, Sandra, Ohlsson, Claes, Gustafsson, Jan-Åke, Dahlman-Wright, Karin
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.03.2008; Portland Press
• Subjects: Adipose Tissue, White - physiology; Ageing, cell death; Animals; Apoptosis Regulatory Proteins - genetics; Biological and medical sciences; Cell physiology; DNA Fragmentation - drug effects; Estradiol - pharmacology; Estradiol - physiology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gene Expression - physiology; Gene Expression Profiling; Glutathione Peroxidase - genetics; Hypothalamus - physiology; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Obesity - genetics; Obesity - physiopathology; Oligonucleotide Array Sequence Analysis; Ovariectomy; Oxidative Stress - physiology; Regular papers; RNA, Messenger - metabolism; Glutathione peroxidase; Adipocyte; Oxidative stress; White adipose tissue; Enzyme; Rodentia; Estrogen; Hypothalamus; Gene expression; Subunit; Ovarian hormone; Encephalon; Fragmentation; Vertebrata; Mammalia; Peroxidases; Mouse; Cell death; Animal; DNA; Hormonal regulation; Oxidoreductases; Sex steroid hormone
• ISSN: 0022-0795; 1479-6805; 1479-6805
• DOI: 10.1677/JOE-07-0277

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 α 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, α-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.