ArticleMolecular metabolism2018
N-terminal transactivation function, AF-1, of estrogen receptor alpha controls obesity through enhancement of energy expenditure.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function.International journal of molecular sciences · 2023Review
- ERK1/2-RSK2 Signaling in Regulation of ERα-Mediated Responses.Endocrinology · 2022Review
- A Novel Mouse Model to Analyze Non-Genomic ERα Physiological Actions.Journal of the Endocrine Society · 2022Review
- The physiological role of estrogen receptor functional domains.Essays in biochemistry · 2021Review
- On the role of sex steroids in biological functions by classical and non-classical pathways. An update.Frontiers in neuroendocrinology · 2021Review
- Erythropoietin Non-hematopoietic Tissue Response and Regulation of Metabolism During Diet Induced Obesity.Frontiers in pharmacology · 2021Review
- A Review on Sex Steroid Hormone Estrogen Receptors in Mammals and Fish.International journal of endocrinology · 2020Review
- Transactivation Function-1-Mediated Partial Agonist Activity of Selective Estrogen Receptor Modulator Requires Homo-Dimerization of the Estrogen Receptor α Ligand Binding Domain.International journal of molecular sciences · 2019Review
- Dysregulation of hypothalamic-pituitary estrogen receptor α-mediated signaling causes episodic LH secretion and cystic ovary.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Risk analysis of systemic levels of estrogen and adipokines as well as estrogen receptors from PBMCs in childbearing and perimenopausal women with obesity.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Obesity-Induced Peritoneal Dissemination of Ovarian Cancer and Dominant Recruitment of Macrophages in Ascites.Immune network · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveStudies using the estrogen receptor alpha (ERα) knock-out (αERKO) mice have demonstrated that ERα plays a crucial role in various estrogen-mediated metabolic regulations. ERα is a ligand dependent transcription regulator and its activity is regulated by estrogenic compounds. ERα consists of two transcriptional activation domains, AF-1 and AF-2. The activities of these domains are regulated through different mechanisms; however, the specific physiological role in metabolic regulation by these domains is still unclear.
methodsWe utilized an ERα AF-2 mutant knock-in mouse (AF2ERKI) to evaluate the physiological functionality of ERα transactivation domains. Due to the estrogen insensitive AF-2 mutation, the phenotypes of AF2ERKI mice are seemingly identical to the global αERKO including obesity in the females. Distinct from the αERKO, the AF-1 function of AF2ERKI mice can be activated by tamoxifen (Tam). Ovariectomized (OVX) AF2ERKI and WT females were treated with Tam and fed a high-fat diet (HFD) for 10 weeks. Additionally, indirect calorimetric analysis was performed using metabolic chambers with food intake and locomotor activity recorded for Tam-treated AF2ERKI and αERKO females.
resultsObesity in HFD-fed AF2ERKI females was prevented by Tam treatment; particularly, inguinal fat accumulation was strongly blocked by Tam treatment. Alterations in fat metabolism genes, however, were not found in either inguinal fat nor visceral fat to be Tam-regulated, even though fat accumulation was strongly reduced by Tam treatment. Indirect calorimetric analysis revealed that without alteration of food intake and locomotor activity Tam treatment increased energy expenditure in AF2ERKI but not αERKO females.
conclusionsThese results suggest that the activation of ERα AF-1 prevents fat accumulation. The prevention of obesity through AF-1 is mediated by induction of energy expenditure rather than ERα AF-1 functionality of lipid metabolism gene regulation in fat tissues.
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