Increased uncoupling protein-2 gene expression in brain of lipopolysaccharide-injected mice: role of tumour necrosis factor-alpha?

In order to understand the role of brain localized uncoupling proteins, we have examined the UCP2 and BMCP-1 gene expression in mice brain in two diff erent catabolic states: administration of lipopolysaccharide (LPS) (2.5 mg/ kg, i.p.) and tumour burden. Administration of LPS resulted in an increased UCP2 gene expression both in brain (208%) and cerebellum (77%). An increas e in UCP2 gene expression was also observed after LPS treatment in double k nockout mice for tumour necrosis factor-cc (TNF) receptors 1 and 2 (75% in brain and 33% in cerebellum). Tumour growth also resulted in increased brai n UCP2 gene expression (80%) in mice bearing the Lewis lung carcinoma as co mpared with the non-tumour-bearing controls. No changes were observed in BM CP-1 mRNA levels of either LPS-injected or tumour-bearing mice. From the re sults presented it may be suggested that: (a) the brain may contribute sign ificantly to the increase in energy expenditure associated with hypermetabo lic states such as fever and tumour burden, and (b) the regulation of UCP2 gene expression in brain does not seem to be influenced by TNF; therefore t he action of other cytokines cannot be discarded. (C) 2001 Elsevier Science B.V. All rights reserved.