PACAP ameliorates hepatic metabolism and inflammation through up-regulating FAIM in obesity

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase-activating polypeptide (PACAP) suppresses anti-inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and tumour necrosis factor alpha (TNF-α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down-regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up-regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK-3β, in the liver of obese mice. However, down-regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti-inflammation, glucose regulation and lipid metabolism in obese liver.