Globular adiponectin decreases leptin-induced tumor necrosis factor-α expression by murine macrophages: Involvement of cAMP-PKA and MAPK pathways

Abstract

Several lines of evidence have supported a link between obesity and inflammation. The present study investigated the capacity of leptin and globular adiponectin to affect tumor necrosis factor alpha (TNF-α) production in murine peritoneal macrophages. Leptin stimulated TNF-α production at mRNA as well as protein levels in a dose- and time-dependent manner. Intracellular cAMP concentration was increased and protein kinase A (PKA) was activated with the treatment of leptin, subsequently downstream MAPK signal proteins, ERK1/2 and p38, were phosphorylated. Specific inhibitors for the signal proteins, Rp cAMPS, H89, PD98059, and U0126, or SB203580, suppressed the signaling pathway and TNF-α expression. Although gAd partially increased cAMP concentration and PKA activity, it directly reduced leptin-induced ERK1/2 and p38 MAPK phosphorylation thus inhibiting TNF-α production. In conclusion, leptin promotes inflammation by stimulating TNF-α production, which is mediated by cAMP-PKA-ERK1/2 and p38 MAPK pathways. gAd inhibited leptin-induced TNF-α production through suppressing phosphorylation of ERK1/2 and p38 pathways.