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Study breakdown

Ghrelin-Blocking Peptide LEAP-2 Is Higher in Girls and Rises During Female Puberty

HumanModerate evidence
The takeaway

LEAP-2 levels are significantly higher in girls than boys regardless of weight status, increase during female puberty (p<0.001), and correlate with insulin, IGF-1, and metabolic markers in a sexually dimorphic pattern.

p<0.001

significance of LEAP-2 increase from prepubertal to pubertal stage in girls

What the researchers found

LEAP-2 is significantly higher in girls vs. boys regardless of obesity status. In girls, LEAP-2 increases significantly during puberty (p<0.001) and correlates positively with insulin, IGF-1, HOMA-IR, triglycerides and negatively with ghrelin.

Why it matters

Understanding LEAP-2's role in puberty could reveal new mechanisms behind sex differences in appetite, metabolism, and pubertal timing. Given LEAP-2's ghrelin-blocking function, this has implications for understanding childhood obesity and pubertal disorders.

The numbers in context

LEAP-2 associated with puberty in girls; modulated by nutritional status; LEAP-2 is endogenous GHSR1a antagonist.

How the study worked

Cross-sectional study of 150 lean and obese children and adolescents. Plasma LEAP-2 measured with comparison by sex, pubertal stage, and body weight. Correlation analysis with metabolic hormones and markers.

Who was studied

Children assessed for LEAP-2 levels in relation to pubertal status and nutrition

What this study cannot tell us

Cross-sectional design cannot establish causation or temporal relationships. Relatively small sample for subgroup analyses. Plasma LEAP-2 levels may not reflect tissue-specific activity. Only one ethnic group studied.

How to read the evidence

Well-powered cross-sectional study (n=150) with clear sex-specific findings. Longitudinal studies needed to establish temporal relationships.

When this study was published

Published in 2021. LEAP-2 biology is a rapidly expanding field with increasing clinical interest.

The bigger picture

LEAP-2 is emerging as a key regulator of the ghrelin system. Its sex-specific changes during puberty suggest it may be involved in the metabolic reprogramming that occurs during female sexual development, connecting appetite regulation to reproductive maturation.

Questions still open

  • Does LEAP-2 contribute to sex differences in appetite and metabolism during adolescence?
  • Could LEAP-2 levels predict early or delayed puberty in girls?
  • Is LEAP-2 involved in the higher obesity rates seen in girls during puberty?

Common questions

What is LEAP-2?
Liver-expressed antimicrobial peptide 2 is a recently discovered hormone that blocks ghrelin's appetite-stimulating effects. It's part of the body's natural appetite regulation system and its levels change with nutritional status.
Why does LEAP-2 matter for puberty?
Puberty involves major metabolic changes including shifts in appetite, body composition, and hormone levels. LEAP-2's dramatic rise during female puberty suggests it may help coordinate these metabolic changes with sexual development.

Read the original research

Circulating LEAP-2 is associated with puberty in girls.

International journal of obesity (2005), 45(3), 502-514

Citation

Barja-Fernández, Silvia; Lugilde, Javier; Castelao, Cecilia; Vázquez-Cobela, Rocío; Seoane, Luisa M; Diéguez, Carlos; Leis, Rosaura; Tovar, Sulay. (2021). Circulating LEAP-2 is associated with puberty in girls.. International journal of obesity (2005), 45(3), 502-514. https://doi.org/10.1038/s41366-020-00703-3