Dual Modulation of Adipogenesis and Lipolysis Augments Facial Adipose Tissue Restoration

Aging leads to structural changes in facial adipose tissue, characterized by an imbalance between adipocyte regeneration and hypertrophy. Current therapeutic approaches primarily target individual aspects of these changes, often failing to address the dual nature of facial adipose remodeling. Using a combination of in vivo and ex vivo methods, we present a therapeutic strategy based on Kaempferia parviflora root extract (KPRE) rich in polymethoxyflavonoids. Mechanistically, we demonstrate that KPRE sustains preadipocyte proliferation while reducing hypertrophy in mature adipocytes via activation of the transcriptional regulators SOX9 and GATA3 while suppressing PPARγ and SREBP1. To translate these findings toward human application, we conducted a clinical pilot study in 35 participants with topical application of KPRE long-chain fatty acid emulsions for 6 months. By comparing high-resolution stereoscopic imaging and digital 3-dimensional modeling data at baseline and after 3 months and 6 months of follow-up, we show significant volume restoration in atrophic regions and reduction in hypertrophic areas, consistent with the coordinated effects observed in the organotypic adipose culture models. These findings provide a successful example for the rapid translation of molecular insights gained from organotypic human tissue models to human application and provide clinical evidence supporting the potential of KPRE-based formulations for facial adipose tissue rejuvenation.