Objective
Circulating levels of liver-enriched antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist, decrease under caloric restriction and increase in obesity. The role of LEAP2 in male puberty, a phase with accelerated energy demand, is unclear.
Methods
We determined circulating LEAP2 levels in 28 boys with constitutional delay of growth and puberty (CDGP) who participated in a randomized controlled trial (NCT01797718), and were treated with letrozole (n=15) or intramuscular low-dose testosterone (T) (n=13) for 6 months. Blood sampling and dual-energy x-ray absorptiometry-measured body composition were performed at 0, 6, and 12 month visits.
Results
Serum LEAP2 levels decreased significantly during pubertal progression (0-6 mo: mean decrease -4.3 [10.3] ng/ml, p=0.036 and 0-12mo: -3.9 [9.3] ng/ml, p=0.033). Between 0 and 6 months, the changes in serum LEAP2 levels correlated positively with changes in percentage of body fat (rs=0.48, p=0.011), and negatively with growth velocity, and estradiol levels (rs=-0.43, p=0.022, rs=-0.55, p=0.003, respectively). In the T group only, the changes in serum LEAP2 correlated negatively with changes in testosterone and estradiol levels. Between 0 and 12 months, the change in LEAP2 levels correlated negatively with the change in HDL levels (rs= -0.44, p=0.022) and positively with the change in insulin (rs=0.50, p=0.009), and HOMA-IR (rs=0.51, p=0.007) levels.
Conclusions
Circulating LEAP2 levels decreased after induction of puberty reciprocally with increased growth rate and energy demand reflecting the metabolic state of the adolescent. Further, the results suggest that estradiol levels may have a permissive role in downregulating circulating LEAP2 levels.