a, b Seventy-two hours fed state or fasting+leptin or fasting+placebo (study 1, n = 13). a Blood concentrations of fatty acid profile from start and till completion of the study as ratios of the baseline (0 day). GC/MS-EI was used to quantify fatty acid methyl esters in whole plasma. b Blood-free fatty acids (FFA) from start and till completion of the study; mixed model was performed (for FFA adjusted for baseline). P values of G (group: fed or fasting + placebo or fasting + leptin), T (time: days of study), and G*T interaction of mixed models are reported. In panels a and b by G*T < 0.05, post hoc Bonferroni test was performed between the estimated means of the three groups and between the three groups at each timepoint. One, two, or three asterisks indicate P < 0.05, <0.01, or <0.001 for fed vs fasting + placebo (red) and for fed vs fasting + leptin (blue). One, two, or three hash signs indicate P < 0.05, <0.01, or <0.001 for fasting + leptin vs fasting + placebo in the Bonferroni post hoc t test. c Open-label long-term leptin treatment in mildly hypoleptinemic women (study 3, n = 7). Blood FFA concentrations. P value of time effect (i.e., days of study) of mixed models adjusted for baseline is reported. Two asterisks indicate P < 0.01 for the specific timepoint vs 0 (baseline) in the Bonferroni post hoc t test (performed by P < 0.05). 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. By G*T < 0.05, post hoc Bonferroni test was additionally performed between the two groups at each timepoint. One or two asterisks indicate P < 0.05, or <0.01 for leptin vs placebo for the specific timepoint. 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 Total FA (ratio) G = 0.008 × 10−4; T = 0.002 × 10−1; fed vs Le = 0.004 × 10−1; day 2 fed vs Pl = 0.008 & fed vs Le = 0.002; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.002. SFA (ratio) G = 0.002 × 10−4; T = 0.003 × 10−2; fed vs Le = 0.008 × 10−5; day 2 fed vs Pl = 0.003 & fed vs Le = 0.002; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.001. MUFA (ratio) G = 0.002 × 10−6; fed vs Le = 0.008 × 10−7; day 1 fed vs Le = 0.021; day 2 fed vs Pl = 0.001 & fed vs Le = 0.001 × 10−1; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.036. PUFA (ratio) T = 0.005 × 10−3. C14:0 (ratio) G = 0.009 × 10−2; Le vs Pl = 0.004 × 10−1; day 3 fed vs Le = 0.002 & Le vs Pl = 0.002. C16:0 (ratio) G = 0.004 × 10−5; T = 0.002 × 10−2; fed vs Le = 0.002 × 10−5; day 2 fed vs Pl = 0.008 × 10−1 & fed vs Le = 0.008 × 10−1; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.002. C16:1 (ratio) G = 0.002 × 10−6; T = 0.004 × 10−2; fed vs Le = 0.007 × 10−7; day 1 fed vs Pl = 0.012; day 2 fed vs Pl = 0.009 & fed vs Le = 0.001 × 10−1; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.014. C18:0 (ratio) day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.008. C18:1n9cis (ratio) G = 0.001 × 10−6; fed vs Le = 0.006 × 10−7; day 1 fed vs Le = 0.022; day 2 fed vs Pl = 0.001 & fed vs Le = 0.001 × 10−1; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.039. C18:2n6cis (ratio) T = 0.001 × 10−1; C20:4n6 (ratio) G = 0.002 × 10−1; T = 0.002 × 10−1; fed vs Le = 0.001 × 10−1; day 2 fed vs Pl = 0.022 & fed vs Le = 0.004; day 3 fed vs Le = 0.001 × 10−1 & Le vs Pl = 0.008 × 10−1. C20:5n3 (ratio) day 2 fed vs Le = 0.025; day 3 fed vs Le = 0.004 & Le vs Pl = 0.038. C20:3n6 (ratio) T = 0.006 × 10−12; C22:0 (ratio) T = 0.005 × 10−6; C22:6n3 (ratio) T = 0.001 × 10−3; day 2 fed vs Pl = 0.004 & fed vs Le = 0.004; day 3 fed vs Le = 0.003 × 10−1 & Le vs Pl = 0.011. b
G = 0.004 × 10−11; T = 0.005 × 10−13; G*T = 0.004 × 10−3; fed vs Le = 0.005 × 10−10; fed vs Pl = 0.003 × 10−6; day 2 fed vs Le 0.002 × 10−7 & fed vs Pl = 0.004 × 10−5; day 3 fed vs Le = 0.008 × 10−9 & fed vs Pl = 0.001 × 10−10. c Post hoc test at 15 days = 0.002. d Post hoc test at 8 weeks = 0.011 and at 16 weeks = 0.002.