The effects of PACAP and related peptides on leptin, soluble leptin receptor and resistin in normal condition and LPS-induced inflammation

Abstract

Leptin and resistin are adipokines considered as pro-inflammatory factors related to metabolic syndrome, inflammatory and/or autoimmune conditions. Pituitary adenylate cyclase activating peptide (PACAP) is a pleiotropic neuropeptide with anti-inflammatory properties. We investigated the influence of PACAP on the serum level of leptin, soluble leptin receptor (SLR) and resistin in ordinary and LPS-induced inflammatory conditions using PACAP38 and a series of selective agonist for each PACAP receptor types. It was found that PACAP exerted opposite effects on the leptin:SLR ratio and the serum resistin level. In ordinary condition, PACAP acted as a pro-inflammatory factor by increasing the leptin:SLR ratio and serum resistin level. But in LPS-induced acute inflammatory condition, PACAP not only antagonized the effects of LPS, but also even reversed the effects of LPS. In mice treated with LPS, co-treatment with PACAP decreased the serum leptin and resistin levels and increased the serum soluble leptin receptor level significantly. It was also found that, in ordinary condition, treatment with PAC1 agonist maxadilan induced marked increase in serum leptin, leptin:SLR ratios and resistin levels; while in LPS-induced inflammation, VPAC1 mediated much more anti-inflammatory and reversing-LPS effects of PACAP on leptin and resistin than PAC1 and VPAC2. It is concluded that different receptors mediates different effects of PACAP on leptin, SLR and resistin in non-inflammatory and LPS-induced inflammatory conditions.