Chronic
inflammation augments the deleterious effects of several diseases, particularly diabetes,
cancer, and
sepsis. It is also involved in the process of metabolic shift from
glucose oxidation to
lactate production. Although several studies suggest that the change in activity of the
pyruvate dehydrogenase complex (PDC) is a major factor causing this metabolic change, the exact mechanism of the inflammatory state remains unclear. In this study, we investigated the effect of
lipopolysaccharide (LPS) on the expression of
pyruvate dehydrogenase kinase 4 (PDK4), which is strongly associated with inactivation of the PDC in C2C12 myoblasts. In C2C12 myoblasts, LPS exposure led to increased PDK4
mRNA and
protein expression levels as well as
lactate production in culture medium. However, the expression levels of other PDK
isoenzymes (PDK1 - 3) remained unchanged. Additionally, we observed that LPS treatment induced phosphorylation of Jun N-Terminal
Kinases (JNK). To confirm the role of JNK, we inhibited the JNK pathway and observed that PDK4 expression and
lactate production were decreased, but p38 and ERK were not significantly changed. Taken together, our results suggest that LPS induces PDK4 expression and alters
glucose metabolism via the JNK pathway.