Platycodon grandiflorus-derived exosome-like nanovesicles drive AMPK-dependent glycolytic beige remodeling to ameliorate obesity
13 affiliations
- 1Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- 2Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- 3Department of Microbiology and Sarcopenia Total Solution Center, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea
- 4College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, Goyang 10326, Republic of Korea
- 5Department of Precision Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- 6Kyung Hee University Korean Medicine Hospital, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea
- 7Korean Medicine-Based Drug Repositioning Cancer Research Center, Kyung Hee University, Seoul 02447, Republic of Korea
- 8NeuroGlymph Imaging and Modulation Center, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea
- 9State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
- 10Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medical Sciences, Hainan Medical University, Haikou 571101, China
- 11Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
- 12Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, USA
- 13Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
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.
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BibTeX
@article{kim2026platycodon,
title = {{Platycodon grandiflorus-derived exosome-like nanovesicles drive AMPK-dependent glycolytic beige remodeling to ameliorate obesity}},
author = {Hye-Lin Kim and Harim Kim and Yohan Han and Suhyeon An and Mina Boo and Hyunyoung Choi and Ji In Park and Hyunwoo Kim and HyunSoo Yang and Jae Heon Sim and Dokyoung Kim and Kwan-Il Kim and Seunghoon Lee and Woojin Kim and Ji Hoon Jung and Jungbin Song and In-Seon Lee and Dong-Hyun Youn and Ki-Sun Park and Ke-Wu Zeng and Wei Huang and Jae-Young Um and Seong-Gyu Ko and Rodrigo W. Alves de Souza and Duo Zhang and Carl J. Hauser and Jinbong Park and Leo E. Otterbein and Hyo In Kim},
journal = {Asian journal of pharmaceutical sciences},
year = {2026},
month = sep,
doi = {10.1016/j.ajps.2026.101198},
url = {https://europepmc.org/article/PMC/PMC13720142},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Platycodon grandiflorus-derived exosome-like nanovesicles drive AMPK-dependent glycolytic beige remodeling to ameliorate obesity
AU - Hye-Lin Kim
AU - Harim Kim
AU - Yohan Han
AU - Suhyeon An
AU - Mina Boo
AU - Hyunyoung Choi
AU - Ji In Park
AU - Hyunwoo Kim
AU - HyunSoo Yang
AU - Jae Heon Sim
AU - Dokyoung Kim
AU - Kwan-Il Kim
AU - Seunghoon Lee
AU - Woojin Kim
AU - Ji Hoon Jung
AU - Jungbin Song
AU - In-Seon Lee
AU - Dong-Hyun Youn
AU - Ki-Sun Park
AU - Ke-Wu Zeng
AU - Wei Huang
AU - Jae-Young Um
AU - Seong-Gyu Ko
AU - Rodrigo W. Alves de Souza
AU - Duo Zhang
AU - Carl J. Hauser
AU - Jinbong Park
AU - Leo E. Otterbein
AU - Hyo In Kim
PY - 2026
DA - 2026/09/07
JO - Asian journal of pharmaceutical sciences
DO - 10.1016/j.ajps.2026.101198
UR - https://europepmc.org/article/PMC/PMC13720142
AB - 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.
SN - 1818-0876
SN - 2221-285X
ER -