Exercise Preserves the Appetite-Suppressing Peptide LEAP2 After Weight Loss in Women | Research

The takeaway

Exercise maintained LEAP2 (an anorexigenic peptide that blocks ghrelin) after diet-induced weight loss in females, potentially preventing the appetite rebound that causes weight regain.

Exercise saves LEAP2
In women, exercise maintained the appetite-suppressing peptide LEAP2 after weight loss — neither liraglutide nor dieting alone did this

What the researchers found

In females, exercise maintained fasting and postprandial LEAP2 during weight maintenance after LCD, while liraglutide did not. In males, LEAP2 decreased with LCD and remained low regardless of intervention. Sex-specific LEAP2 regulation.

Why it matters

Weight regain after dieting is the rule. Understanding that exercise preserves an appetite-suppressing peptide (LEAP2) in women provides a biological rationale for exercise during weight maintenance.

How the study worked

Sub-analysis of 128-person (79F, 49M) RCT: LCD weight loss → 1-year maintenance randomized to exercise, liraglutide, combination, or placebo. LEAP2 measured fasting and during 3h meal tests.

What this study cannot tell us

Sex-stratified analysis not pre-specified. Small subgroups. LEAP2 is a relatively new biomarker. Cannot prove LEAP2 preservation causes less weight regain.

How to read the evidence

Sub-analysis of RCT with sex-stratified findings. Novel but hypothesis-generating.

When this study was published

Published in 2025.

The bigger picture

LEAP2 may be the missing link explaining why exercise prevents weight regain — it preserves an anti-hunger peptide that dieting alone depletes.

Questions still open

Does LEAP2 preservation directly predict less weight regain?
Why does exercise preserve LEAP2 in females but not males?
Could LEAP2 agonists be developed as weight maintenance drugs?

Common questions

What is LEAP2?

LEAP2 is a liver-produced peptide that blocks ghrelin (the hunger hormone). When you diet, LEAP2 drops, making you hungrier. Exercise uniquely keeps LEAP2 levels high in women, potentially preventing diet-driven appetite rebound.

Why does exercise prevent weight regain?

This study suggests a specific mechanism: exercise preserves LEAP2, a peptide that suppresses appetite by blocking ghrelin. This biological effect adds to the calorie-burning benefits of exercise.

Read the original research

Exercise maintains LEAP2 levels after weight loss in females with obesity.

iScience, 29(1), 114288

View on PubMed ↗Publisher’s paper ↗

Citation

Holt, Joachim; Holm, Stephanie K; Sandsdal, Rasmus M; Jensen, Simon B K; Juhl, Christian R; Noer, Mikkel H; Afshar-Bahadori, Yasmin; Blond, Martin B; Gerds, Thomas A; Stallknecht, Bente M; Madsbad, Sten; Holst, Jens J; Holst, Birgitte; Hartmann, Bolette; Byberg, Sarah; Torekov, Signe S. (2026). Exercise maintains LEAP2 levels after weight loss in females with obesity.. iScience, 29(1), 114288. https://doi.org/10.1016/j.isci.2025.114288