Abstract Energy metabolism is subject to reprogramming in the body upon bacterial or virus infection. It is generally believed that immune cells sense the stress signals of infection to mediate the reprogramming of whole-body energy metabolism. However, the key molecules required for the immune cell function remain to be identified. In this study, we addressed the issue by examining the energy metabolism in Lyz2-p65-KO mice, in which p65 (RelA) gene is inactivated in myeloid cells. On Chow diet, the p65-KO mice exhibited no difference to the wild type mice in the energy metabolism. On a high fat diet (HFD), the KO mice gained less adipose tissue and body weight for improved insulin sensitivity and blood lipids along reduction in pro-inflammatory cytokine. This was observed with more energy loss in feces. The KO mice showed a reduction in metabolic rate after LPS challenge for accelerated decrease of oxygen consumption. They had a high mortality rate in the septic shock model with less elevation of serum pro-inflammatory cytokines and more elevation of anti-inflammatory cytokines. In vitro, the KO macrophages expressed less pro-inflammatory cytokines in response to stimulation by palmitic acid, IL-1β and TNF-α. In conclusion, the data suggest that p65 is a key molecule in myeloid cells to mediate the reprogramming of energy metabolism under stress conditions of HFD feeding.
Wang et al. (Tue,) studied this question.