Obesity Disrupts Liver's Metabolic Timing Without Damaging Core Molecular Network

A research team from the University of Tokyo has discovered that obesity disrupts the liver's ability to coordinate metabolic responses during fasting, while the organ's underlying molecular network structure remains intact. The findings, published in Science Signaling, offer new insights into the dynamics of energy metabolism.

Energy metabolism is essential for maintaining physiological homeostasis, and fasting represents a significant stress test to this balance. As a central metabolic organ, the liver must precisely regulate the timing of molecular activations to cope with energy deficits. However, due to a historical lack of comprehensive time-series data, the mechanisms behind this coordination have remained poorly understood.

In this study, researchers compared liver function in healthy and obese mice and found significant differences in key regulatory molecules. Healthy mice exhibited the presence of ATP and AMP—crucial molecules for energy regulation—while these were absent in obese mice. Notably, despite this absence, the structural integrity of the molecular networks remained unaffected in obese mice. The core issue, the researchers found, lies in disrupted temporal coordination: whereas healthy livers respond swiftly and sequentially to fasting, obese livers lose this orderly timing entirely.

By integrating molecular network structures with time-based analysis, this study introduces a novel framework for exploring metabolic regulation. The approach holds promise for broader applications, including studies on feeding states and metabolic disorders.