Exercise maintains LEAP2 levels after weight loss in females with obesity
Liver-expressed antimicrobial peptide 2 (LEAP2) is an anorexigenic hormone, but its long-term decrease after diet-induced weight loss may promote weight regain. This study examined whether exercise, glucagon-like peptide-1 receptor agonist (GLP-1RA) (liraglutide), or their combination prevents the post-diet decrease in LEAP2 during 1 year of weight-loss maintenance. LEAP2 plasma levels were measured in the fasting state and during 3-h standard liquid meal tests (600 kcal) in a randomized, double-blinded, placebo-controlled trial. 128 adults with obesity were included (BMI: 36.9 ± 2.9 kg/m<sup>2</sup>), 79 females and 49 males. Sex differences were evident at data inspection. In males, fasting LEAP2 decreased during the low-calorie diet (LCD) (<i>p</i> < 0.001), while in females, there was a delayed decrease after 1 year in the placebo, liraglutide, and combination groups (<i>p</i> < 0.001 to 0.033). Interestingly, in females in the exercise group, fasting and postprandial LEAP2 levels remained high. These findings raise the possibility that exercise might preserve LEAP2 levels after weight loss in females, supporting weight-loss maintenance.
Authors
- Rasmus Michael Sandsdal (ORCID: https://orcid.org/0000-0003-0590-6285)
- Birgitte Holst (ORCID: https://orcid.org/0000-0001-7432-097X)
- Mikkel H. Noer (ORCID: https://orcid.org/0000-0001-6008-4507)
- Signe S. Torekov (ORCID: https://orcid.org/0000-0001-6779-0252)
- Christian R. Juhl (ORCID: https://orcid.org/0000-0003-3024-4017)
- Bolette Hartmann (ORCID: https://orcid.org/0000-0001-8509-2036)
- Sten Madsbad (ORCID: https://orcid.org/0000-0002-5017-1815)
- Bente Stallknecht (ORCID: https://orcid.org/0000-0003-3117-0451)
- Sarah Byberg (ORCID: https://orcid.org/0000-0002-7363-4595)
- Joachim Holt (ORCID: https://orcid.org/0009-0005-1307-9680)
- Simon Birk Kjær Jensen (ORCID: https://orcid.org/0000-0002-1437-2150)
- Thomas Alexander Gerds (ORCID: https://orcid.org/0000-0002-5955-816X)
- Stephanie Holm (ORCID: https://orcid.org/0000-0002-9628-8285)
- Martin Bæk Blond (ORCID: https://orcid.org/0000-0002-2032-1560)
- Jens J Holst
- Yasmin Afshar-Bahadori
Institutions
- University of Copenhagen (DK)
- Steno Diabetes Centers (DK)
- Hvidovre Hospital (DK)
Publication Details
- Journal
- iScience
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1016/j.isci.2025.114288
- Primary Topic
- Diabetes Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Hjerteforeningen
- Lundbeckfonden
- Novo Nordisk
- Helsefonden
- Novo Nordisk Fonden
- H. Lundbeck A/S