Yu Rongjie, Xie Shanshan, Chen Jiansu, Zhang Ling, Dai Yun
Engineering Institute of Jinan University, Jinan University, Guangzhou, PR China.
Peptides. 2009 Aug;30(8):1456-9. doi: 10.1016/j.peptides.2009.05.013. Epub 2009 May 22.
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.
瘦素和抵抗素是被认为与代谢综合征、炎症和/或自身免疫性疾病相关的促炎因子。垂体腺苷酸环化酶激活肽（PACAP）是一种具有抗炎特性的多效性神经肽。我们使用PACAP38和一系列针对每种PACAP受体类型的选择性激动剂，研究了PACAP在正常和脂多糖（LPS）诱导的炎症条件下对瘦素、可溶性瘦素受体（SLR）和抵抗素血清水平的影响。结果发现，PACAP对瘦素:SLR比值和血清抵抗素水平产生相反的影响。在正常条件下，PACAP通过增加瘦素:SLR比值和血清抵抗素水平而作为一种促炎因子。但在LPS诱导的急性炎症条件下，PACAP不仅拮抗LPS的作用，甚至还能逆转LPS的作用。在用LPS处理的小鼠中，与PACAP共同处理可显著降低血清瘦素和抵抗素水平，并增加血清可溶性瘦素受体水平。还发现，在正常条件下，用PAC1激动剂马克西迪兰处理可导致血清瘦素、瘦素:SLR比值和抵抗素水平显著升高；而在LPS诱导的炎症中，VPAC1介导的PACAP对瘦素和抵抗素的抗炎和逆转LPS作用比PAC1和VPAC2更强。得出的结论是，在非炎症和LPS诱导的炎症条件下，不同的受体介导PACAP对瘦素、SLR和抵抗素的不同作用。
