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Estrogen Controls Lipolysis by Up-Regulating α2A-Adrenergic Receptors Directly in Human Adipose Tissue through the Estrogen Receptor α. Implications for the Female Fat Distribution
Abstract
Estrogen seems to promote and maintain the typical female type of fat distribution that is characterized by accumulation of adipose tissue, especially in the sc fat depot, with only modest accumulation of adipose tissue intraabdominally. However, it is completely unknown how estrogen controls the fat accumulation. We studied the effects of estradiol in vivo and in vitro on human adipose tissue metabolism and found that estradiol directly increases the number of antilipolytic α2A-adrenergic receptors in sc adipocytes. The increased number of α2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on α2A-adrenergic receptor mRNA expression was observed in adipocytes from the intraabdominal fat depot. These findings show that estrogen lowers the lipolytic response in sc fat depot by increasing the number of antilipolytic α2A-adrenergic receptors, whereas estrogen seems not to affect lipolysis in adipocytes from the intraabdominal fat depot. Using estrogen receptor subtype-specific ligands, we found that this effect of estrogen was caused through the estrogen receptor subtype α. These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic α2A-adrenergic receptors only in sc and not in visceral fat depots. Thus, our findings offer an explanation how estrogen maintains the typical female sc fat distribution because estrogen seems to inhibit lipolysis only in sc depots and thereby shifts the assimilation of fat from intraabdominal depots to sc depots.
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“Although the mechanisms behind the hormonal regulation of AT distribution are complex and still incompletely characterized, they may arise from effects on lipolysis and lipogenesis, adipocyte differentiation, and insulin sensitivity [9,24,[28][29][30].”
From Adipose tissue estrogen production and metabolism in premenopausal women (2021) · cites this paper as [28]
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“estrogen upregulates α2-adrenergic receptors in abdominal subcutaneous adipocytes (55).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [55]
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“Estradiol directly increases the number of antilipolytic α2A-adrenergic receptors in subcutaneous adipocytes [69].”
From Estrogen deficiency and the origin of obesity during menopause (2014) · cites this paper as [69]
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Metadata
- Authors
- Pedersen, S. B., Kristensen, K., Hermann, P. A., Katzenellenbogen, J. A., & Richelsen, B.
- Affiliations
- Aarhus University Hospital (DK)
- University of Illinois Urbana-Champaign (US)
- Aarhus University (DK)
- Corresponding author
- Pedersen, Steen B.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-04-01
- Volume
- 89
- Issue
- 4
- Pages
- 1869-1878
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2068408721
- Cited by
- 276
- References
- 50
- Citations by year
- 2026: 6 · 2025: 23 · 2024: 19 · 2023: 16 · 2022: 15 · 2021: 19 · 2020: 17 · 2019: 15 · 2018: 12 · 2017: 16 · 2016: 6 · 2015: 10 · 2014: 15 · 2013: 8 · 2012: 11
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK015556)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- estrogen, estradiol, lipolysis, alpha2A-adrenergic receptor, estrogen receptor alpha, subcutaneous adipose tissue, visceral adipose tissue, epinephrine, adipocyte metabolism, receptor up-regulation
- MeSH terms
- Abdomen, Adipose Tissue, Adrenergic alpha-Antagonists, Sterol Esterase, Estradiol, Estrogens, Female, Humans, Lipolysis, Lipoprotein Lipase, Receptors, Adrenergic, Receptors, Estrogen, RNA, Messenger, Sex Characteristics, Yohimbine, Up-Regulation, Adipocytes, Receptors, Adrenergic, alpha-2, Subcutaneous Tissue, Estrogen Receptor alpha, In Vitro Techniques
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