Estrogen Sulfotransferase Inhibits Adipocyte Differentiation
Open accessAbstract
The estrogen sulfotransferase (EST) is a phase II drug-metabolizing enzyme known to catalyze the sulfoconjugation of estrogens. EST is highly expressed in the white adipose tissue of male mice, but the role of EST in the development and function of adipocytes remains largely unknown. In this report, we showed that EST played an important role in adipocyte differentiation. EST was highly expressed in 3T3-L1 preadipocytes and primary mouse preadipocytes. The expression of EST was dramatically reduced in differentiated 3T3-L1 cells and mature primary adipocytes. Overexpression of EST in 3T3-L1 cells prevented adipocyte differentiation. In contrast, preadipocytes isolated from EST knockout (EST−/−) mice exhibited enhanced differentiation. The inhibitory effect of EST on adipogenesis likely resulted from the sustained activation of ERK1/2 MAPK and inhibition of insulin signaling, leading to a failure of switch from clonal expansion to differentiation. The enzymatic activity of EST was required for the inhibitory effect of EST on adipogenesis, because an enzyme-dead EST mutant failed to inhibit adipocyte differentiation. In vivo, overexpression of EST in the adipose tissue of female transgenic mice resulted in smaller adipocyte size. Taken together, our results suggest that EST functions as a negative regulator of adipogenesis.
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EST is expressed in adipose tissue and reduces adipocyte size, although overexpression of EST in subcutaneous and visceral adipose tissue may induce insulin resistance.
“EST is expressed in adipose tissue and reduces adipocyte size, although an overexpression of EST in sc and visceral adipose tissue may induce insulin resistance.”
From Estrogen deficiency and the origin of obesity during menopause (2014) · cites this paper as [127]
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References 46 · Cited by 54
- Authors
- Wada, T., Ihunnah, C. A., Gao, J., Chai, X., Zeng, S., Philips, B. J., Rubin, J. P., Marra, K. G., & Xie, W.
- Affiliations
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences (T.W., C.A.I., J.G., X.C., W.X.) and Division of Plastic Surgery
- Zhejiang University (CN)
- University of Pittsburgh (US)
- Corresponding author
- Xie, Wen
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2011-09-01
- Volume
- 25
- Issue
- 9
- Pages
- 1612-1623
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC3165918
- OpenAlex
- W2130330533
- Cited by
- 54
- References
- 46
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- University of Pittsburgh
- Government of Jiangxi Province
- China Scholarship Council
- National Institutes of Health
- National Cancer Institute (R01CA114246, CA114246)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK083953)
- National Institute of Environmental Health Sciences (R01ES014626, ES014626)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- estrogen sulfotransferase, adipogenesis, white adipose tissue, 3T3-L1 preadipocytes, ERK signaling, insulin signaling, clonal expansion, estrogen sulfation, adipocyte size
- MeSH terms
- Adipose Tissue, Animals, Cell Differentiation, Enzyme Activation, Estradiol, Female, Insulin, Male, Mice, Inbred C57BL, Mice, Transgenic, RNA, Messenger, Sulfotransferases, Signal Transduction, Gene Expression Regulation, Enzymologic, Gene Deletion, Adipocytes, 3T3-L1 Cells, PPAR gamma, Extracellular Signal-Regulated MAP Kinases, Cell Size, Adipogenesis, Mice
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