Mechanistic study of FA-PG3 nanoparticles promoting adipose browning through the PPARγ and PRDM16-UCP1 pathway in severe pediatric obesityDownload PDF Download PDF ArticleOpen accessPublished: 18 June 2026Xiaoli Zhang1 na1,Yuan Tian2 na1,Shengqun Xu2 &…Dan Zhang3 npj Science of Food (2026) Cite this article We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.SubjectsBiochemistryBiotechnologyCell biologyAbstractFood-derived bioactive compounds offer an attractive and sustainable approach to metabolic disease prevention, yet mechanistic evidence supporting their efficacy in pediatric obesity remains limited. This study investigates the thermogenic potential of ferulic acid (FA), a plant-derived phenolic compound, when delivered via a dendrimer-based nanocarrier. Using an integrative strategy combining network pharmacology, molecular docking, cellular assays, animal models, and clinical biomarker analysis, we demonstrate that FA-loaded generation 3 PAMAM nanoparticles (FA-PG3) effectively activate adipose tissue thermogenesis. Computational analyses identified UCP1 as a central molecular target of FA, with PPARγ and PRDM16 acting as critical upstream regulators. FA-PG3 nanoparticles exhibited optimized nanoscale properties and sustained FA release. In vitro, FA-PG3 promoted beige adipocyte differentiation, enhanced mitochondrial respiration, and increased thermogenic gene expression. In vivo, FA-PG3 improved energy expenditure, insulin sensitivity, and adipose browning in obese mice, while UCP1 silencing largely abolished these metabolic benefits. Notably, children with severe obesity exhibited significantly lower circulating levels of browning-associated adipokines, supporting the clinical relevance of targeting thermogenic pathways. Our findings highlight a previously underappreciated food-derived, nano-enabled strategy for metabolic reprogramming and position FA-PG3 as a promising translational candidate for addressing pediatric obesity through adipose tissue thermogenesis.The alternative text for this image may have been generated using AI.AcknowledgementsNo funding was received for this research.Author informationAuthor notesThese authors contributed equally: Xiaoli Zhang, Yuan Tian.Authors and AffiliationsDepartment of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, ChinaXiaoli ZhangDepartment of Otorhinolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaYuan Tian & Shengqun XuDepartment of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, ChinaDan ZhangAuthorsXiaoli ZhangView author publicationsSearch author on:PubMed Google ScholarYuan TianView author publicationsSearch author on:PubMed Google ScholarShengqun XuView author publicationsSearch author on:PubMed Google ScholarDan ZhangView author publicationsSearch author on:PubMed Google ScholarCorresponding authorsCorrespondence to Shengqun Xu or Dan Zhang.Ethics declarationsCompeting interestsThe authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary information41538_2026_865_MOESM1_ESM (download PDF )Rights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsAbout this articleDownload PDF