From Virtual Screening to Functional Compound Repurposing: New Approaches to Enhance Adiponectin for Metabolic Health
Event Info
2025-11-20
11:00 AM
Lecture Theater F (Lift 25/26), HKUST
Abstract
Adiponectin is a key regulator of metabolic health, yet strategies to effectively enhance its signaling remain limited. In this talk, I will present two innovative approaches to address this challenge. First, using virtual screening, we identified Parthenolide (PNL), a natural sesquiterpene lactone, as a novel dual agonist of adiponectin receptors AdipoR1 and AdipoR2. Chronic PNL administration in high-fat diet-fed mice significantly improved obesity, hepatic steatosis, and insulin resistance. Mechanistic studies demonstrated that PNL directly activates hepatic AdipoR1/R2 signaling via the APPL1 pathway, enhances AMPK/PPAR-α signaling in adipose tissue, and improves insulin sensitivity in adipocytes. Second, we developed a robust high-throughput screening (HTS) platform utilizing OP9 cells with an adiponectin promoter-driven luciferase reporter, and discovered that pazopanib, an FDA-approved anti-cancer drug, acts as a potent adiponectin enhancer. Pazopanib enhances adiponectin in mature adipocytes as well as enhances adipogenesis with different mechanisms. In a mouse model of cancer cachexia, accelerated the recovery of fat mass and muscle endurance, elevated adiponectin levels and reduced adipose tissue fibrosis, identifies pazopanib’s new function as a metabolic enhancer besides its anti-tumor role. Together, these studies not only introduce promising new modulators of adiponectin signaling but also demonstrate the power and utility of our screening platform for the discovery of novel therapeutic compounds targeting metabolic disorders.
Biography
Dr. Zhu Yuyan is currently an Associate Professor in the Department of Food Science and Nutrition at The Hong Kong Polytechnic University (PolyU). She earned her Bachelor’s degree from Zhejiang University and her PhD from Purdue University, USA. Afterwards, she conducted postdoctoral training at the Georgia Institute of Technology (USA) where she played a key role in multiple NIH-funded research projects. At PolyU, she established her lab working on obesity and associated metabolic disorders, with the focus on adipose tissue, including cholesterol homeostasis in adipocytes during adipose tissue expansion, the role of adipose tissue remodeling in regulating systemic energy metabolism, and develop the dietary/pharmaceutical strategies to ameliorate obesity and its associated metabolic disorders. As Principal Investigator, she leads multiple projects on glucose and lipid metabolism. She has published first/corresponding-author papers in SCI-indexed journals such as Metabolism, Journal of Lipid Research (JLR), Journal of Hazardous Materials (JHM), and Advanced Functional Materials (Adv. Funct. Mater.). Her collaborative work has appeared in Cell, Nature Neuroscience, Advanced Science, and PNAS etc. She has been granted several patents covering methods for the treatment of obesity.