Research Projects

The rising global epidemic of obesity and metabolic disorders demands innovative therapeutic strategies to enhance energy expenditure by promoting white adipose tissue (WAT) browning, a process in which lipid-storing white adipocytes acquire thermogenic features resembling brown or beige adipocytes. Although compounds like pterostilbene (PTER) and resveratrol (RESV) have shown promise in inducing WAT browning via AMPK/SIRT1/PGC-1α-mediated mitochondrial biogenesis, their mechanistic depth remains incomplete, particularly regarding organelle-level metabolic adaptations. This study aims to bridge this gap by exploring two novel and interconnected aspects: (1) the role of cytoophidia-mitochondria interactions in WAT browning, where cytoophidia, filamentous structures formed by CTP synthase (CTPS) regulate intracellular CTP and nucleotide availability critical for mitochondrial DNA replication and biogenesis, and (2) stilbenoids and their derivatives as modulators of cytoophidia-mitochondria dynamics, with a focus on PTER-ITC, a hybrid molecule combining PTER’s browning effects with the anti-inflammatory properties of isothiocyanates, as well as newly developed derivatives to enhance efficacy. The study also addresses unresolved questions in WAT browning research, such as the nucleotide sources fueling mitochondrial expansion and the unexplored role of cytoophidia in adipocyte metabolism, while leveraging nanoparticle-based delivery systems to overcome the poor solubility and bioavailability of stilbenoids. Anticipated outcomes include mechanistic insights into how cytoophidia support mitochondrial biogenesis, identification of PTER-ITC or other derivatives as lead anti-obesity compounds, and broader implications for organelle communication in metabolic diseases. This work is highly innovative, introducing cytoophidia as a new player in WAT browning, advancing next-generation stilbenoid derivatives, and offering a translatable therapeutic strategy with potential for rapid clinical application given stilbenoids' established safety profile. By integrating cell biology, metabolomics, and drug design, this study will provide groundbreaking insights into obesity treatment, positioning cytoophidia-mitochondria interactions and PTER derivatives as key targets in metabolic therapeutics.