L-carnitine

A nutritional modulator of glucocorticoid receptor functions.

Salvatore Alesci, Massimo U. De Martino, Marco Mirani, Salvatore Benvenga, Francesco Trimarchi, Tomoshige Kino, George P. Chrousos

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

L-carnitine is an essential nutrient with a major role in cellular energy production. There is evidence that, at high doses, L-carnitine might mimic some of the biological activities of glucocorticoids, especially immunomodulation. To explore the molecular basis of this effect, we tested the influence of L-carnitine on glucocorticoid receptor-alpha (GRalpha) functions. Millimolar concentrations of L-carnitine, which were not cytotoxic in vitro, significantly reduced the whole cell binding of [3H]dexamethasone to GRalpha by decreasing the affinity of this receptor for its steroid ligand. At the same concentrations, L-carnitine was able to trigger nuclear translocation of green fluorescent protein (GFP)-fused human GRalpha and transactivate the glucocorticoid-responsive mouse mammary tumor virus (MMTV) and TAT3 promoters in a dose-dependent fashion. This effect was solely dependent on the presence of glucocorticoid-responsive elements on the promoter and on the expression of functional GRalpha by the cell. Finally, similarly to glucocorticoids, L-carnitine suppressed tumor necrosis factor-alpha (TNFalpha) and interleukin-12 release by human primary monocytes stimulated with lipopolysaccharide ex vivo. Both GRalpha transactivation and cytokine suppression by L-carnitine were abrogated by the GRalpha-antagonist RU 486. Taken together, our results suggest that pharmacological doses of L-carnitine can activate GRalpha and, through this mechanism, regulate glucocorticoid-responsive genes, potentially sharing some of the biological and therapeutic properties of glucocorticoids.

Original languageEnglish
Pages (from-to)1553-1555
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number11
Publication statusPublished - 2003
Externally publishedYes

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Carnitine
Glucocorticoid Receptors
Modulators
Glucocorticoids
Mouse mammary tumor virus
Mifepristone
Immunomodulation
Steroid Receptors
Interleukin-12
Green Fluorescent Proteins
Bioactivity
glucocorticoid receptor alpha
Viruses
Dexamethasone
Transcriptional Activation
Nutrients
Lipopolysaccharides
Tumors
Monocytes
Tumor Necrosis Factor-alpha

Cite this

L-carnitine : A nutritional modulator of glucocorticoid receptor functions. / Alesci, Salvatore; De Martino, Massimo U.; Mirani, Marco; Benvenga, Salvatore; Trimarchi, Francesco; Kino, Tomoshige; Chrousos, George P.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 17, No. 11, 2003, p. 1553-1555.

Research output: Contribution to journalArticle

Alesci, Salvatore ; De Martino, Massimo U. ; Mirani, Marco ; Benvenga, Salvatore ; Trimarchi, Francesco ; Kino, Tomoshige ; Chrousos, George P. / L-carnitine : A nutritional modulator of glucocorticoid receptor functions. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003 ; Vol. 17, No. 11. pp. 1553-1555.
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