Leptin promoted glycolytic metabolism to induce DCs activation via
STAT3-HK2 pathway
Abstract
Leptin is over-secreted in many autoimmune diseases, which can promote
dendritic cells (DCs) maturation and up-regulate the expression of
inflammatory cytokines, but the underlying mechanisms are not fully
elucidated. Considering the major role of leptin in maintaining energy
balance and the significant role of glycolysis in DCs activation, our
study aims to investigate whether leptin promotes the activation of DCs
via glycolysis and its underlying mechanisms. We demonstrated that
leptin promoted the activation of DCs, including up-regulating the
expression of co-stimulatory molecules and inflammatory cytokines,
enhancing the proliferation and T helper 17 (Th17) cell ratio in
peripheral blood mononuclear cells (PBMC) co-cultured with
leptin-stimulated DCs. Leptin also enhanced DCs glycolysis with
increased glucose consumption, lactate production, and the expression of
hexokinase 2 (HK2). In addition, the activation of DCs stimulated by
leptin could be inhibited by the glycolysis inhibitor 2-DG. To explore
the signaling pathways involved in leptin-induced HK2 expression, we
observed that only the inhibitors of STAT3 (NSC74859) could repress the
enhancement of HK2 triggered by leptin stimulation. Therefore, our
results indicated that leptin promoted glycolytic metabolism to induce
DCs activation via STAT3-HK2 pathway.