P65 inactivation in adipocytes and macrophages attenuates adipose inflammatory response in lean but not in obese mice

NF-κB induces transcriptional expression of proinflammatory genes and antiapoptotic genes. The two activities of NF-κB remain to be characterized in the mechanism of chronic inflammation in obesity. To address this issue, we inactivated NF-κB in adipose tissue by knocking out p65 (RelA) in mice (F-p65-KO) and examined the inflammation in lean and obese conditions. In the lean condition, KO mice exhibited a reduced inflammation in adipose tissue with a decrease in macrophage infiltration, M1 polarization, and proinflammatory cytokine expression. In the obese condition, KO mice had elevated inflammation with more macrophage infiltration, M1 polarization, and cytokine expression. In the mechanism of enhanced inflammation, adipocytes and macrophages exhibited an increase in cellular apoptosis, which was observed with more formation of crown-like structures (CLS) in fat tissue of KO mice. Body weight, glucose metabolism, and insulin sensitivity were not significantly altered in KO mice under the lean and obese conditions. A modest but significant reduction in body fat mass was observed in KO mice on HFD with an elevation in energy expenditure. The data suggest that in the control of adipose inflammation, NF-κB exhibits different activities in the lean vs. obese condition. NF-κB is required for expression of proinflammatory genes in the lean but not in the obese condition. NF-κB is required for inhibition of apoptosis in the obese condition, in which proinflammation is enhanced by NF-κB inactivation.