PEA release by pNAPE-LP + palmitate decreases pro-inflammatory mediators’ expression in the mouse colon and their release in the plasma through a selective PPARα involvement in DSS-treated mice. The administration of pNAPE-LP associated to palmitate (0.0003 μg/kg) induced a significant reduction in iNOS, COX-2 and IL-1β protein expression, as well as NO, PGE2, IL-1β and TNFα levels through PPARα-dependent involvement in mice colon and plasma. (A) Western blot analysis of iNOS, COX-2 and IL-1β protein expression and (B–D) relative densitometric analysis (arbitrary units normalized on the expression of the housekeeping protein β-actin). (E–H) Respective quantification of NO2−, PGE2, IL-1β and TNFα levels in mice plasma showing the effects of pNAPE-LP associated to palmitate (0.0003 μg/kg), given alone or in the presence of MK886 (10 mg/kg) or GW9662 (1 mg/kg) in the colonic tissue of DSS-treated mice. Results are expressed as the mean ± SD of n = 5 experiments performed in triplicate. *** p < 0.001 versus vehicle; °°° p < 0.001 versus DSS-treated mice.