Faculty, Staff and Student Publications
Language
English
Publication Date
10-24-2025
Journal
Science Advances
DOI
10.1126/sciadv.ady7904
PMID
41124259
PMCID
PMC12542948
PubMedCentral® Posted Date
10-22-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis of tissue fibrosis. Here, we report the x-ray crystal structures of a leptin-neutralizing antibody (hLep3) in the unbound and leptin-bound states. The interaction of this antibody with leptin mimics the interaction of the LEPR with leptin, providing direct insights into the mechanism by which the antibody disrupts leptin signaling. We furthermore evaluate the therapeutic potential of neutralizing leptin with this antibody across distinct mouse models of fibrosis affecting the kidney, liver, lung, heart, and blood vessels. Leptin neutralization markedly inhibited fibrosis progression in all models. Mechanistically, suppression of leptin activity reduces pro-inflammatory and profibrotic processes, underscoring its therapeutic potential. These findings suggest that leptin signaling plays a vital role in tissue fibrosis and that treatment with a leptin-neutralizing antibody may be a promising therapeutic approach.
Keywords
Leptin, Animals, Mice, Receptors, Leptin, Fibrosis, Antibodies, Neutralizing, Signal Transduction, Humans, Disease Models, Animal, Protein Binding
Published Open-Access
yes
Recommended Citation
Sun, Xue-Nan; Chen, Shiuhwei; Zhao, Shangang; et al., "Leptin as a Key Driver for Organ Fibrogenesis" (2025). Faculty, Staff and Student Publications. 5267.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5267
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