Exp Mol Med.  2002 Nov;34(5):353-360.

Retinoic acid inhibits inducible nitric oxide synthase expression in 3T3-L1 adipocytes

• Yang JY
• Koo BS
• Kang MK
• Rho HW
• Sohn HS
• Jhee EC
• Park JW

Abstract

The present study was undertaken to explore whether retinoids, which are known to have immunomodulatory actions, could attenuate tumor necrosis factor-alpha (TNF)-stimulated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 adipocytes. Adipocytes incubated with TNF induced dose- and time-dependent accumulation of nitrite in the culture medium through the iNOS induction as confirmed by Western blotting. Treatment of cells with TNF in the presence of all-trans-retinoic acid (RA) significantly decreased their ability to produce nitrite and iNOS induction. Both 13-cis- and all- trans-RA-induced suppression was dose-dependent, and all-trans-RA was somewhat potent than 13-cis-RA. The inhibitory effect of RA on TNF-induced iNOS induction was reversible, completely recovered after 2 days, and was exerted through the inhibition of NF-kappaB activation. TNF also suppressed the lipoprotein lipase (LPL) activity of 3T3-L1 adipocytes. RA could not reverse the TNF- induced LPL suppression at RA levels causing near complete inhibition of the TNF-induced NO production. These results indicate that RAs attenuate iNOS expression reversibly in TNF-stimulated 3T3-L1 adipocytes, and that the TNF- induced LPL suppression is not the result of NO overproduction.

Keyword

adipocytes; retinoic acid receptors; nitric oxide; nitric oxide synthase; tretinoin; tumor necroses factor

MeSH Terms

3T3 Cells
Adipocytes/drug effects/*enzymology/metabolism
Animals
Cells, Cultured
Enzyme Induction/drug effects
Enzyme Inhibitors/pharmacology
Lipoprotein Lipase/drug effects/metabolism
Mice
NF-kappa B/antagonists & inhibitors
Nitric Oxide/metabolism
Nitric-Oxide Synthase/*antagonists & inhibitors/*metabolism
Tretinoin/*pharmacology
Tumor Necrosis Factor/pharmacology