Sex Differences in Angiogenic Ligand and Receptor Protein Expression During Adipose Tissue Expansion and Regression

Inadequate angiogenesis in obesogenic adipose tissue (AT) has been implicated in disrupted adipogenesis and metabolic disorders. While several regulators of AT angiogenesis have been identified, our understanding of the quantitative changes in angiogenic signaling proteins during obesity progression remains incomplete, particularly regarding sex-specifi c responses. This study sought to identify the dysregulated elements within the Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF) systems during obesity progression.

We employ a mouse model, comprising both male and female mice, to investigate the changes in the VEGF/PDGF concentration and their receptor distribution in gonadal AT during short- and long-term weight gain and weight loss.

Female mice preserve adipose tissue angiogenic signatures during obesity progression, including sustained upregulation of endothelial VEGFR1 protein, maintenance of VEGF-A levels and endothelial cell populations, and differential regulation of PDGF levels, compared to males. These sex-specifi c patterns correlate with improved adipose expandability and may contribute to the more metabolically healthy obesity phenotype commonly observedin females.

These sex-specifi c patterns correlate with improved adipose expandability and may contribute to the more metabolically healthy obesity phenotype commonly observed in females. Our quantitative profi ling also lays the groundwork for developing computational models of VEGF/PDGF signaling networks in AT, allowing for the simulation of complex biological interactions and the prediction of therapeutic outcomes.

The online version contains supplementary material available at https://doi.org/10.1007/s12195-026-00925-x.