Activation of the classical I?B kinases (IKK? and IKK?) was previously shown to contribute to obesity-induced inflammation and insulin resistance. Using knockout mice, we investigated whether the related isoform IKK? plays a similar metabolic role. IKK?(-/-) mice had reduced body weight, leptin levels, as well as higher insulin sensitivity when kept on chow diet. However, inflammatory parameters, measured in liver, adipose tissue and plasma, were either unaltered or showed a trend toward up-regulation (liver NF-?B activity, TNF? and IL-1? expression). Chronic feeding of a high fat diet induced equal obesity and insulin resistance, and similarly induced inflammatory markers, in IKK?(-/-) and wild-type mice, indicating that under high caloric conditions the inflammatory and metabolic effects of IKK? deficiency were overridden. Taken together, our data indicate that IKK? does not have general pro-inflammatory properties in liver and adipose tissue, and suggest that reduced adiposity is the primary mechanism for improved insulin sensitivity in IKK?(-/-) mice on chow diet.
