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Originally published In Press as doi:10.1194/jlr.M400344-JLR200 on October 1, 2004

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Journal of Lipid Research, Vol. 46, 135-142, January 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Inducible nitric oxide synthase modulates lipolysis in adipocytes

Patrice Penfornis and André Marette1

Department of Anatomy-Physiology, Lipid Research Unit, Laval University Hospital Center, Québec, G1V 4G2, Canada

1 To whom correspondence should be addressed. e-mail: andre.marette{at}crchul.ulaval.ca

The role of inducible nitric oxide synthase (iNOS) in the modulation of adipocyte lipolysis was investigated. Treatment of white and brown adipose cell lines and mouse adipose explants with a mixture of tumor necrosis factor-{alpha}, interferon-{gamma}, and lipopolysaccharide (LPS) doubled the lipolytic rate, and this was associated with marked induction of iNOS expression and nitric oxide (NO) production. iNOS inhibition by 1400W, aminoguanidine, or L-NIL pretreatment further increased the cytokine/LPS-mediated lipolysis by 30% (P < 0.05) in cultured adipocytes and in adipose explants. However, this potentiating effect of iNOS inhibition was abolished in adipose explants isolated from iNOS knockout mice. Pharmacological inhibitors of adenylyl cyclase or protein kinase A reduced cytokine/LPS-induced lipolysis and also blunted the potentiating effect of iNOS inhibition on the lipolytic rate. Furthermore, addition of the antioxidants L-cystine and L-glutathione to cytokine/LPS-stimulated adipocytes mimicked the lipolytic effect of iNOS inhibition.

In conclusion, inhibition of iNOS activity in adipocytes potentiates cytokine/LPS-induced lipolysis. This effect was fully reversed by adenylyl cyclase and protein kinase A inhibitors but was mimicked by cellular antioxidants. These data suggest that iNOS-mediated NO production counteracts cytokine/LPS-mediated lipolysis in adipocytes and that this feedback mechanism involves an oxidative process upstream of cAMP production in the signaling pathway.

Supplementary key words adipose tissue • cytokines • lipopolysaccharide • adenylyl cyclase • protein kinase A • perilipin • hormone-sensitive lipase • antioxidants


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Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1068 - E1077.
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