iNOS as a metabolic enzyme under stress conditions

Nitric oxide (NO) is a free radical acting as a cellular signaling molecule in many different biochemical processes. NO is synthesized from L-arginine through the action of the nitric oxide synthase (NOS) family of enzymes, which includes three isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS). iNOS-derived NO has been associated with the pathogenesis and progression of several diseases, including liver diseases, insulin resistance, obesity and diseases of the cardiovascular system. However, transient NO production can modulate metabolism to survive and cope with stress conditions. Accumulating evidence strongly imply that iNOS-derived NO plays a central role in the regulation of several biochemical pathways and energy metabolism including glucose and lipid metabolism during inflammatory conditions. This review summarizes current evidence for the regulation of glucose and lipid metabolism by iNOS during inflammation, and argues for the role of iNOS as a metabolic enzyme in immune and non-immune cells.