Deciphering the dynamical origin of the Adipogenic commitment during stress-induced disruption of the circadian rhythm
Year: 2026
Type: preprint
Abstract: Obesity is a major health concern worldwide and is caused by an excessive fat accumulation in the body due to adipogenesis. Recent studies suggest that excessive stress or disruption of circadian rhythms can enhance adipogenic commitment and lead to obesity. Moreover, this adipogenic commitment occurs at a specific time of day, highlighting a correlation with the circadian rhythm. However, the dynamical nature of this kind of stress-induced adipogenic differentiation remains an unresolved puzzle. Herein, we proposed a mathematical model centred on the key transcription factor PPARγ, associated with adipogenic differentiation, and demonstrated that adipogenic commitment is a bistable, irreversible differentiation process in which slow positive feedback regulation of PPARγ primarily controls the differentiation commitment threshold. The model reproduced the experimental observations regarding the extent of adipogenesis induced by constant and pulsatile stress input signals and explained the correlation between adipogenic differentiation time and circadian phase. It further predicts how to control the adipogenic commitment even under stressful conditions. Overall, our study elucidates how stress signalling dynamically governs adipogenesis.
Authors: Debjit Das, Kajal Charan, Sandip Kar
Institution: Indian Institute of Technology Bombay
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213977588