FIGURE 6.

The effects of long-term (28-day) treatment with ASK1476 (starting dose 30 nmol/kg day, then increase to 60 and finally 120 nmol/kg/d) or oxytocin (OXT; 600 nmol/kg/d) on weight gain and food intake in DIO rats. Long-term reductions of body weight were observed in both ASK1476 and OXT treatment groups without compensatory weight regain (A). OXT 600 nmol/kg/d yielded significantly greater reductions in body weight than ASK1476 at both the 30 nmol/kg and 60 nmol/kg doses, however, the effect of ASK1476 dosed at 120 nmol/kg/d was more comparable (B). Both ASK1476 and OXT treated animals resisted compensatory weight gain throughout the 28-d treatment period with significantly lower rates of weight regain following body weight nadir (C). Post-treatment body composition analyses indicated no difference in either percent lean or fat mass relative to vehicle for either OXT or ASK1476 (D). ASK1476 120 nmol/kg/d was similarly effective as oxytocin 600 nmol/kg/d at attenuating caloric intake across the 28-day experiment (E). Food intake remained significantly reduced across the 28-day treatment for both OXT and ASK1476 (F) with the two treatments yielding comparable effects on cumulative food intake (G). Post hoc analyses with p-values adjusted for multiple comparisons: **p < 0.01; ***p < 0.001; ****p < 0.0001.