Nitric oxide: a new player in the modulation of energy metabolism

Nitric oxide (NO) is a key messenger molecule in several cell types. NO for mation is catalyzed by a family of NO synthases (NOS) that use L-arginine a s a substrate. Rat adipose tissue expresses the inducible, macrophage-type, nitric oxide (NO) synthase isoform (iNOS), Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) markedly increases the express ion and activity of iNOS in both white and brown adipose tissues, as well a s in skeletal muscle. iNOS induction can be reproduced in vitro by treatmen t of cultured white or brown adipocytes or L6 myocytes with LPS and inflamm atory cytokines (TNF alpha, IFN gamma). The physiological role of NO in adi pose tissues and skeletal muscle is still obscure. Recent evidence suggests that NO may be implicated in the regulation of energy metabolism. Using bo th pharmacological and genetic models of iNOS invalidation, we have recentl y begun to uncover a role for NO in the modulation of glucose transport and lipoprotein hydrolysis. These studies support the emerging concept that NO may fulfill the dual role of modulating energy metabolism in both physiolo gical and pathological conditions as well as contributing to local immune d efense during inflammatory processes.