Platycodon grandiflorus-derived exosome-like nanovesicles drive AMPK-dependent glycolytic beige remodeling to ameliorate obesity
Year: 2026
Type: article
Abstract: Obesity is a pandemic with limited therapeutic options. Recent pharmacotherapies are constrained by tolerability, durability, accessibility, and incomplete resolution of adipose tissue dysfunction. Plant-derived exosome-like nanovesicles (ELNs) provide a natural nanoscale therapeutic platform. However, their anti-obesity effects and underlying mechanisms remain unexplored. In the present study, we investigated whether ELNs from Platycodon grandiflorus roots (P-ELNs) can mitigate obesity. P-ELNs were isolated, characterized and evaluated in high-fat diet-induced and genetic (db/db) obesity models. Analyses integrating transcriptomic profiling and metabolic flux assessment were performed to define the P-ELN-induced adipose remodeling program. Treatment with P-ELNs significantly attenuated body weight gain and reduced white adipose tissue (WAT) mass in obese mice without inducing systemic, hepatic or renal toxicity. Mechanistically, P-ELNs enhanced non-shivering thermogenesis in inguinal WAT through AMP-activated protein kinase (AMPK)-dependent remodeling toward a glycolytic beige fat state characterized by the coordinated activation of myogenic and glycolytic gene programs. Collectively, P-ELNs represent a safe and effective nanotherapeutic strategy to combat obesity through AMPK-dependent glycolytic beige fat remodeling. Therefore, P-ELNs are a first-in-class nanotherapeutic that induce this unique beige fat subtype, providing a novel strategy to treat obesity and related metabolic disorders.
Authors: Hye-Lin Kim, Harim Kim, Yohan Han, Suhyeon An, Mina Boo, Hyunyoung Choi, Ji In Park, Hyunwoo Kim, HyunSoo Yang, Jae Heon Sim, Dokyoung Kim, Kwan-Il Kim, Seunghoon Lee, Woojin Kim, Ji Hoon Jung, Jungbin Song, In-Seon Lee, Dong-Hyun Youn, Ki-Sun Park, Ke-Wu Zeng, Wei Huang, Jae-Young Um, Seong-Gyu Ko, Rodrigo W. Alves de Souza, Duo Zhang, Carl J. Hauser, Jinbong Park, Leo E. Otterbein, Hyo In Kim
Institutions: Dongguk University, Kyung Hee University, Pusan National University, Wonkwang University, Kyung Hee University Medical Center, Kyung Hee University Korean Medicine Hospital, Korea Institute of Oriental Medicine, Peking University, State Key Laboratory of Natural and Biomimetic Drugs, Hainan Medical University, Beth Israel Deaconess Medical Center, Harvard University, University of Georgia, Charlie Norwood VA Medical Center
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Awards: G4480260281, G653715803, G8838826325
OpenAlex ID: W7211908543
