POS8-1179
Exercise-Mimetic Multi-Organ Device Recapitulates Myokine-Mediated Inter-Organ Metabolic Crosstalk in Obesity-Induced T2DM
Topic
S8. Frontiers of Functional Polymers in Biology and Medicine
When and Where
Sep 30, 2026
08:30 - 09:30
Room 301 (Grand Ballroom)
Session Chairs
Heesuk KIM
Jinhye BAE
Presenter(s)
Yerim Jung (Incheon National University)
Co-Author(s)
Abstract
Obesity-induced type 2 diabetes mellitus (T2DM) is a multi-organ metabolic disease driven by dysregulated crosstalk among the liver, pancreas, and skeletal muscle. Exercise regulates multi-organ metabolic homeostasis via myokines, representing a leading non-pharmacological therapy. However, conventional in vitro models mostly rely on recombinant proteins or conditioned media, limiting their ability to recapitulate the real-time secretion and circulation of myokines during exercise.
In this study, we integrated skeletal muscle (C2C12), liver (HepG2), and pancreas (INS-1E) into a single microfluidic multi-organ device (MOD), in which peristaltic pump-driven flow established a vascular-like inter-organ connection. A palmitic acid (PA)-induced lipotoxic T2DM model was established, followed by electrical pulse stimulation (EPS) of the muscle constructs to mimic exercise. EPS increased Myh1 expression, and time-resolved analysis revealed a transient IL-6 secretion profile—an initial increase followed by a decline—recapitulating exercise-induced myokine kinetics.
The exercise-derived IL-6 was delivered to the liver and pancreas via continuous circulation within the MOD. In HepG2 spheroids, PA-induced lipid accumulation decreased by ~30%, Fetuin-A secretion decreased, and albumin secretion increased, indicating improved hepatic function. In INS-1E spheroids, ROS levels decreased and insulin secretion was enhanced, confirming exercise-mediated inter-organ metabolic regulation.
Collectively, the exercise-mimetic MOD provides a physiologically relevant platform for reproducing the real-time secretion of exercise-derived myokines and the resulting inter-organ metabolic regulation, serving as a valuable in vitro model for investigating obesity-induced T2DM pathophysiology and evaluating exercise-based therapeutic strategies.
This work was supported by the NRF (2022R1C1C1008610 and RS-2025-02243019), KFRM (24A0105L1 and 22A0105L1) and the KIMST (RS-2026-25541458).
In this study, we integrated skeletal muscle (C2C12), liver (HepG2), and pancreas (INS-1E) into a single microfluidic multi-organ device (MOD), in which peristaltic pump-driven flow established a vascular-like inter-organ connection. A palmitic acid (PA)-induced lipotoxic T2DM model was established, followed by electrical pulse stimulation (EPS) of the muscle constructs to mimic exercise. EPS increased Myh1 expression, and time-resolved analysis revealed a transient IL-6 secretion profile—an initial increase followed by a decline—recapitulating exercise-induced myokine kinetics.
The exercise-derived IL-6 was delivered to the liver and pancreas via continuous circulation within the MOD. In HepG2 spheroids, PA-induced lipid accumulation decreased by ~30%, Fetuin-A secretion decreased, and albumin secretion increased, indicating improved hepatic function. In INS-1E spheroids, ROS levels decreased and insulin secretion was enhanced, confirming exercise-mediated inter-organ metabolic regulation.
Collectively, the exercise-mimetic MOD provides a physiologically relevant platform for reproducing the real-time secretion of exercise-derived myokines and the resulting inter-organ metabolic regulation, serving as a valuable in vitro model for investigating obesity-induced T2DM pathophysiology and evaluating exercise-based therapeutic strategies.
This work was supported by the NRF (2022R1C1C1008610 and RS-2025-02243019), KFRM (24A0105L1 and 22A0105L1) and the KIMST (RS-2026-25541458).
