Fig. 1. Metabolic inflammatory complex: a new concept.

In the previous linear model, inflammatory response induces metabolic alterations under stressful conditions, such as sepsis, and inflammatory response and metabolic alterations are viewed as upstream and downstream events, respectively. In contrast, recently accumulating evidence indicates that metabolic inflammatory complex can be viewed as the nexus of a network consisting of positive feedback and feed-forward mechanisms relating to inflammatory response and metabolic alterations. Crosstalk within the metabolic inflammatory complex takes place at multiple levels, including reciprocal enhancement of the transcriptional activities of NF-κB and HIF-1α. Moreover, mitochondrial dysfunction and disintegrity, which lie at the crossroads of metabolism and inflammatory response, play crucial roles in the development of metabolic inflammatory complex. HIF indicates hypoxia-inducible factor; NF, nuclear factor.