Figure 7. The PGE₂/Treg axis is indispensable for the antiinflammatory and insulin-sensitizing effects of IF.

HFD-fed COX-2–KO mice were fed on an IF schedule or Ad for 4 weeks. Two weeks after IF, mice were injected with PGE₂ or vehicle (Veh) for 2 weeks. (A) PGE₂ administration resulted in significantly decreased body mass of COX-2–KO mice under both IF and Ad conditions. n = 5–8/group. Treatment with PGE₂ restored the AT Treg population (B) and the proportion of Tregs in CD4⁺ cells (C) in COX-2–KO mice under both IF and Ad conditions. n = 4/group. PGE₂ administration improved glucose (D) and insulin (E) tolerance in COX-2–KO mice under both IF and Ad conditions. *P < 0.05 and **P < 0.01 for Veh vs. PGE₂ with Ad diet; ^#P < 0.05 for Ad vs. IF with Veh treatment; ^$P < 0.05 and ^$$P < 0.01 for IF Veh vs. IF PGE₂. HFD-fed C57BL/6 mice were administered CD25 neutralizing antibody for 2 days, followed by PGE₂ injection. (F) Blocking the Treg pathway had no significant effect on the antiobesity effect of PGE₂, as indicated by the body mass. n = 5–8/group. (G and H) Neutralization of CD25 diminished the inducing effects of PGE₂ on the AT Treg population. n = 5/group. Blocking the Treg pathway impaired basal and PGE₂-increased glucose (I) and insulin (J) tolerance. *P < 0.05 and **P < 0.01 for Veh vs. PGE₂; ^#P < 0.05 and ^##P < 0.01 for Ctrl vs. anti-CD25 (aCD25); ^$P < 0.05 and ^$$P < 0.01 for aCD25 vs. PGE₂ aCD25. (K) Working model. ANOVA was used to analyze the data in this figure. All data are reported as mean ± SEM. LN, lymph node.