ADM2 up-regulates UCP1 expression in adipocyte mainly through the CRLR·RAMP1-cAMP/PKA and p38 MAPK pathways. Rat scWAT SVCs were differentiated into adipocytes and treated with ADM2. A and E, Relative mRNA levels of Ucp1 in adipocytes treated with ADM2 for 8 h with or without 1-h pretreatment of CRLR-RAMP receptor antagonists (A) or signaling pathway inhibitors (E). B, cellular cAMP levels. C and D, immunoblotting analysis of phosphorylation levels of PKA-mediated substrates (C) and p38 MAP kinase (D) in adipocytes. The data are represented as the mean ± S.E. n = 3 independent experiments (3–6 samples/experiment). One-way ANOVA with Newman-Keuls test (A and E) or two-tailed Student's t test (B): *, p < 0.05 versus control; **, p < 0.01 versus control; #, p < 0.05 versus ADM2 treatment; ##, p < 0.01 versus ADM2 treatment.