Cited by 293Lipid metabolism and biosynthesisAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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Direct Effect of Glucocorticoids on Lipolysis in Adipocytes

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Xu, Chong, He, Jinhan, Jiang, Hongfeng, Zu, Luxia, Zhai, Wenjie, Pu, Shenshen, Xu, Guoheng·2009·Molecular Endocrinology

DOI 10.1210/me.2008-0464PMC PMC5419195

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Abstract

Hypercortisolemia and glucocorticoid treatment cause elevated level of circulating free fatty acids (FFAs). The basis of this phenomenon has long been linked to the effect of glucocorticoids permitting and enhancing the adipose lipolysis response to various hormones. In this study, we demonstrate that glucocorticoids directly stimulate lipolysis in rat primary adipocytes in a dose- and time-responsive manner; this lipolytic action was attenuated by treatment with the glucocorticoid antagonist RU486. Dexamethasone down-regulates mRNA and protein levels of cyclic-nucleotide phosphodiesterase 3B, thereby elevating cellular cAMP production and activating protein kinase A (PKA). On inhibition of PKA but not other kinases, the lipolysis response ceases. Furthermore, dexamethasone induces phosphorylation and down-regulation of perilipin, a lipid droplet-associating protein that modulates lipolysis; this effect is restored by RU486 or PKA inhibitor H89. Dexamethasone up-regulates mRNA and protein levels of hormone-sensitive lipase (HSL) and adipose triglyceride lipase; these effects, parallel to increased lipolysis, are attenuated by RU486 or actinomycin D. Phosphorylation at Ser-563 and Ser-660 residues of HSL and activity of cellular lipases are elevated on dexamethasone stimulation but abrogated by the coaddition of H89. However, dexamethasone does not induce HSL translocation to the lipid droplet surface in differentiated adipocytes. We show that elevated FFA concentration in plasma is associated with increased lipase activity and lipolysis in vivo in adipose tissues of dexamethasone-treated rats. Therefore, the lipolytic action of glucocorticoids liberates FFA efflux from adipocytes to the bloodstream, which could be a cellular basis of systemic FFA elevation in response to glucocorticoid challenge.

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Authors: Xu, C., He, J., Jiang, H., Zu, L., Zhai, W., Pu, S., & Xu, G.
Affiliations: Peking University (CN)
Zhengzhou University (CN)
Corresponding author: Xu, Guoheng
ORCID: He, Jinhan
Jiang, Hongfeng
Zhai, Wenjie
Xu, Guoheng
Venue: Molecular Endocrinology
Publisher: The Endocrine Society
Published: 2009-08
Volume: 23
Issue: 8
Pages: 1161-1170
ISSN: 0888-8809 (ISSN-L)
1944-9917
DOI: 10.1210/me.2008-0464
PMC: PMC5419195
OpenAlex: W2115274616
Cited by: 291
References: 46
Citations by year: 2026: 12 · 2025: 13 · 2024: 22 · 2023: 22 · 2022: 14 · 2021: 20 · 2020: 21 · 2019: 20 · 2018: 16 · 2017: 26 · 2016: 22 · 2015: 16 · 2014: 16 · 2013: 17 · 2012: 17
FWCI: 6.00
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Molecular Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Pittsburgh
National Natural Science Foundation of China (30770803, 30890042, 30670779)
Peking University
National Key Research and Development Program of China (2006CB 503910, 2009CB941603)
Peking University Health Science Center
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: glucocorticoids, dexamethasone, adipocyte lipolysis, free fatty acids, cyclic AMP, protein kinase A, PDE3B, perilipin, hormone-sensitive lipase, adipose triglyceride lipase, hypercortisolism, RU486, H89, lipid droplets
MeSH terms: Adipose Tissue, Animals, Dexamethasone, Dose-Response Relationship, Drug, Enzyme Inhibitors, Glucocorticoids, Isoquinolines, Lipolysis, Male, Models, Biological, Serine, Sulfonamides, Rats, Sprague-Dawley, Adipocytes, Rats, Cyclic Nucleotide Phosphodiesterases, Type 3

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Direct Effect of Glucocorticoids on Lipolysis in Adipocytes

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