Obesity Alters Molecular Timing in Liver Response to Starvation in Mice

**April 22, 2025 — Researchers from the University of Tokyo have uncovered a significant disruption in how obese mice’s livers respond to starvation at the molecular level. Led by Keigo Morita and Shinya Kuroda, the study reveals that although the structural integrity of the molecular network remains intact during starvation, its temporal coordination is compromised in obese animals. This groundbreaking discovery highlights the importance of time-based analysis in understanding metabolic responses, particularly in obesity.

The team’s research focused on the liver, a central organ in managing metabolism, which coordinates the timing and activity of various molecules to maintain energy balance — a process called homeostasis. During starvation, these molecular networks should respond rapidly and in an organized fashion. In healthy mice, hub molecules like ATP and AMP respond swiftly, orchestrating the body’s adaptation to food scarcity.

However, in obese mice, the study observed a lack of this rapid response, despite the overall structure of the network remaining stable. This indicates that obesity specifically affects the timing—or reaction time—of molecular responses rather than their presence or absence.

By analyzing multi-omic data over time, the researchers constructed a starvation-responsive molecular network that was structurally resilient but temporally vulnerable in obese livers. They found that the normal quick response of hub molecules was slowed or disrupted in obese mice, suggesting a loss of effective temporal regulation.

This discovery was achieved through innovative methods that combined structural and temporal analyses, providing a new perspective on how obesity affects metabolic processes. The approach can be applied to other biological systems and conditions, opening pathways for future research into food intake, disease progression, and metabolic adaptability.

The findings, published in Science Signaling, emphasize that maintaining proper timing in molecular responses is crucial for metabolic health. As obesity increasingly impacts global health, understanding these temporal dynamics offers potential for developing targeted therapies to restore proper metabolic regulation during starvation or other stress conditions.

This study enhances our understanding of the molecular basis of obesity and its effects on the body's adaptive mechanisms, offering promising angles for tackling metabolic disorders in the future.

Source: https://medicalxpress.com/news/2025-04-obesity-disrupts-molecular-reaction-starvation.html

For more details, visit the original publication in Science Signaling.