Cited by 93Lipid metabolism and disordersPeroxisome Proliferator-Activated ReceptorsLipid metabolism and biosynthesis

Metabolic Effects of Rexinoids: Tissue-Specific Regulation of Lipoprotein Lipase Activity

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Davies, Peter J. A., Berry, Stacey A., Shipley, Gregory L., Eckel, Robert H., Hennuyer, Nathalie, Crombie, Diane L., Ogilvie, Kathleen M., Peinado-Onsurbe, Julia +4 more·2001·Molecular Pharmacology

Abstract

Hypertriglyceridemia is a frequent complication accompanying the treatment of patients with either retinoids or rexinoids, [retinoid X receptor (RXR)-selective retinoids]. To investigate the cellular and molecular basis for this observation, we have studied the effects of rexinoids on triglyceride metabolism in both normal and diabetic rodents. Administration of a rexinoid such as LG100268 (LG268) to normal or diabetic rats results in a rapid increase in serum triglyceride levels. LG268 has no effect on hepatic triglyceride production but suppresses post-heparin plasma lipoprotein lipase (LPL) activity suggesting that the hypertriglyceridemia results from diminished peripheral processing of plasma very low density lipoproteins particles. Treatment of diabetic rats with rexinoids suppresses skeletal and cardiac muscle but not adipose tissue LPL activity. This effect is independent of changes in LPL mRNA. In C2C12 myocytes, LG268 suppresses the level of cell surface (i.e., heparin-releasable) LPL activity without altering LPL mRNA. This effect is very rapid (t(1/2) = 2 h) and is blocked by the transcriptional inhibitor actinomycin D. These studies demonstrate that RXR ligands can have dramatic effects on the post-translational processing of LPL and suggest that skeletal muscle may be an important target of rexinoid action. In addition, these data underscore that the metabolic consequences of RXR activation are distinct from either retinoic acid receptor or peroxisome proliferator-activated receptor activation.

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Crossref · 10.1124/mol.59.2.170

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  • Retinoids such as isotretinoin and the anticancer drug bexarotene increase triglyceride levels.

    “An increase in hepatic VLDL and apoC-III production and perhaps a decrease in LpL leading to increased triglyceride levels are also seen during use of retinoids such as isotretinoin and the anticancer drug bexarotene (110 -112).”

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Authors
Davies, P. J. A., Berry, S. A., Shipley, G. L., Eckel, R. H., Hennuyer, N., Crombie, D. L., Ogilvie, K. M., Peinado-Onsurbe, J., Fievet, C., Leibowitz, M. D., Heyman, R. A., & Auwerx, J.
Affiliations
Centre National de la Recherche Scientifique (FR)
Venue
Molecular Pharmacology
Publisher
Elsevier BV
Published
2001-02-01
Volume
59
Issue
2
Pages
170-176
ISSN
  • 0026-895X (ISSN-L)
  • 1521-0111
OpenAlex
W1917585691
Cited by
89
References
44
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 11
FWCI
5.61
Type
journal article
Language
en
Open access
Locations
  • Molecular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
rexinoids, retinoid X receptor, lipoprotein lipase, hypertriglyceridemia, LG100268, post-translational regulation, VLDL, skeletal muscle, myocardium, adipose tissue, diabetic rats, triglyceride metabolism, actinomycin D, retinoids
MeSH terms
Animals, Cells, Cultured, Heart, Lipoprotein Lipase, Lipoproteins, VLDL, Myocardium, Nicotinic Acids, Rats, Zucker, Retinoids, Tetrahydronaphthalenes, Transcription Factors, Triglycerides, Hypertriglyceridemia, Rats, Sprague-Dawley, Receptors, Retinoic Acid, Muscle, Skeletal, Retinoid X Receptors, Rats

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