Chronic administration of ZP5461 does not alter long-term body weight in HFD-fed rats, irrespective of CTR-KD. ZP5461 was peripherally administered every 96 h for 4 wk, first at 1 nmol/kg/mL (dotted arrow) and then at 2 nmol/kg/mL (dashed arrow). A: body weight change across 4 wk of injection treatments; total change in body weight from treatment day 0 to day 28 (A, inset). B: daily noncumulative change in body weight and cumulative change in body weight across the experiment (C); total cumulative change in body weight from treatment day 0 to day 28 (C, inset). Data represented as means ± SE. Control virus, AAV-Control; CTR knockdown virus, AAV-CTR-KD. AAV-Control, vehicle (n = 6), AAV-Control, ZP5461 (n = 7), AAV-CTR-KD, vehicle (n = 8), AAV-CTR-KD, ZP5461 (n = 9). Data analyzed by two-way ANOVA at each time point with Newman–Keuls post hoc analyses. Color of the significance symbols indicates associated cohort; * vs. AAV-Control, vehicle-treated; ^ vs. AAV-CTR-KD, vehicle-treated; # vs. AAV-Control, ZP5461-treated. CTR, calcitonin receptor; HFD, high-fat diet.