Leptin administration in physiological or pharmacological doses does not alter circulating irisin levels in humans

Abstract

Leptin is an adipokine causing browning of adipose tissue, and it thus increases energy expenditure. The same is true for irisin. We studied whether exogenously administered metreleptin affects serum irisin concentrations in humans, which would suggest a direct interplay between leptin and irisin. We performed two studies: a dose-escalating 1-day-long study and a randomized placebo-controlled study. Study 1: 15 healthy, normal-weight and/or obese male and female individuals participated in three 1-day-long trials of metreleptin administration in the fed state. Metreleptin was administered once at physiological and pharmacological (0.01, 0.1 and 0.3 mg per kg body weight) doses. Study 2: 18 apparently healthy hypoleptinemic young women with hypoleptinemia and secondary amenorrhea took part in this study. Subjects received either metreleptin in replacement doses (0.08 and/or 0.12 mg kg(-1)) or placebo for 16 weeks. Blood samples were analyzed for leptin and irisin. We found no effect of metreleptin administration on irisin levels of subjects studied at either the fasting or the fed state either in the short or the long term. We provide evidence that leptin is not altering circulating irisin levels in humans.

Figure 1.

Serum irisin levels in response to metreleptin treatment. (a) Circulating leptin and (b) irisin concentrations of the overall group, after one dose of metreleptin (either 0.01, 0.1 or 0.3 mg per kg body weight) at 0800 hours. (c) Circulating leptin and (d) irisin concentrations after metreleptin (0.08 and/or 0.12 mg kg⁻¹) or control administration on a daily basis between 1900 and 2300 hours for 16 weeks in hypoleptinemic women. The arrow indicates the time when metreleptin was administered. AUC and IAUC were compared using two-sided univariate analysis of variance using Bonferroni’s post hoc test for comparing one intervention to another.