Cytokine-induced metabolic effects in human adipocytes are independent of endogenous nitric oxide

• Published in: American journal of physiology: endocrinology and metabolism Vol. 290; no. 6; pp. E1068 - E1077
• Main Authors: Linscheid, Philippe, Seboek, Dalma, Zulewski, Henryk, Scherberich, Arnaud, Blau, Nenad, Keller, Ulrich, Muller, Beat
• Format: Journal Article
• Language: English
• Published: United States 01.06.2006
• Subjects: Adipocytes - metabolism; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adolescent; Adult; Aged; Biopterins - analogs & derivatives; Biopterins - biosynthesis; Cytokines - metabolism; Cytokines - pharmacology; Drug Synergism; Glycerol - metabolism; Humans; Insulin - physiology; Mesenchymal Stem Cells - metabolism; Middle Aged; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; PPAR gamma - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00374.2005

1 Department of Research, 2 Division of Endocrinology, Diabetology, and Clinical Nutrition, 3 Institute for Surgical Research and Hospital Management, University Hospital, CH-4031 Basel; and 4 Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Zurich, Switzerland Submitted 11 August 2005 ; accepted in final form 20 December 2005 Nitric oxide (NO) has been recognized as a potential mediator of inflammation-induced metabolic alterations, including insulin resistance. However, expression mechanisms and potential roles of endothelial and inducible NO synthases (eNOS and iNOS, respectively) in human adipocytes are poorly understood. In the present study, we aimed to analyze several aspects of NO-related gene expression and metabolite synthesis in basal and inflammation-activated human adipocyte models. eNOS mRNA was highly expressed in omental and to a lesser extent in human subcutaneous adipose tissue biopsies, but not in purified adipocytes, in mesenchymal stem cell (MSC)- and in preadipocyte-derived adipocytes, respectively. Trace amounts of iNOS mRNA were detected in adipose tissue samples of donors with abdominal infection, as opposed to noninfected subjects. Interferon- , in combination with interleukin-1 or lipopolysaccharide, evoked a transient (4 h < time < 24 h) iNOS mRNA expression in human MSC and preadipocyte-derived adipocytes, respectively. This induction was preceded by cytokine-specific mRNAs. In addition, it was accompanied by an activation of the tetrahydrobiopterin synthesis pathway and by inhibition of peroxisome proliferator-activated receptor- 2. In contrast to murine 3T3-L1-derived adipocytes, iNOS protein and NO oxidation products remained undetectable in iNOS mRNA-positive human adipocytes. Accordingly, coadministration of NOS inhibitors (i.e., N -nitro- L -arginine methyl ester, N -monomethyl- L -arginine, and 1400W) had no effects on insulin-mediated glucose uptake and lipolysis. We conclude that, in human adipocytes, endogenous NO is not involved in metabolic regulation during either basal or cytokine-activated conditions. adipose tissue; nitric oxide synthase; insulin resistance; cytokines; lipolysis Address for reprint requests and other correspondence: P. Linscheid, Dept. of Research, Univ. Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland (e-mail: Philippe.Linscheid{at}unibas.ch )