a Seventy-two hours fed state or fasting+leptin or fasting + placebo (study 1, n = 13). Left: blood aldosterone and cortisol at the start and completion of the study. Right: 24-h urine cortisol, epinephrine, and norepinephrine collected at the last day of the study. P values of G (group: fed or fasting + placebo or fasting + leptin), T (time: days of study), and G*T interaction of mixed models, adjusted for baseline are reported. For urine catecholamines, P values were calculated with repeated measure ANOVA, since only the group factor existed. By G*T < 0.05 (blood aldosterone and cortisol) and by G < 0.05 (urine catecholamines), post hoc Bonferroni test was performed between the estimated means of the three groups and between the three groups at each timepoint. Three asterisks indicate P < 0.001 for fed vs fasting + placebo (red) and for fed vs fasting + leptin (blue) at the particular timepoint. b Seventy-two hours of fasting treated with escalating leptin doses (study 2, n = 15). P values of D (dose: 0.01 or 0.1 or 0.3 mg/kg/d), T (time: days of fasting), and D*T interaction of mixed models adjusted for baseline are reported. No post hoc Bonnferroni test was performed since D*T > 0.05. c Open-label long-term leptin treatment in mildly hypoleptinemic women (study 3, n = 7). P value (P) of time effect (i.e., days of study) of mixed models adjusted for baseline is reported. By P < 0.05 post hoc Bonferroni’s test for each timepoint compared to baseline was additionally performed and two asterisks indicate P < 0.01 for the specific timepoint vs 0 (baseline). d Placebo-controlled long-term leptin treatment in mildly hypoleptinemic women (study 4, n = 19 (leptin = 10; placebo = 9)). P values of G (group: placebo or leptin), T (time: weeks of study), and G*T interaction of mixed models adjusted for baseline are reported. No post hoc Bonnferroni test was performed since G*T > 0.05. For Bonferroni post hoc tests, only significant results are reported. All P values are two-sided. Data are demonstrated as means ± SEMs. Exact P values: a aldosterone T = 0.001 × 10−3; day 3 post hoc test for fed vs Pl = 0.004 × 10−2; fed vs Le = 0.006 × 10−2. b Aldosterone T = 0.001 × 10−15; renin T = 0.005 × 10−17; urine epinephrine T = 0.004 × 10−1. c Aldosterone post hoc test at 15 days = 0.005.