A groundbreaking study conducted by researchers at the University of Tokyo has unveiled a critical insight into how obesity affects liver metabolism during periods of starvation. The research reveals that while the molecular structure of the metabolic network remains intact in obese mice, their ability to maintain precise temporal coordination is compromised. In contrast, healthy mice exhibit a well-coordinated sequence of metabolic responses, driven by key molecules such as ATP and AMP. This discovery highlights the importance of timing in metabolic regulation and introduces a novel method for analyzing biological networks over time.
According to the principal investigator, Shinya Kuroda, cells within the liver form an intricate network where specific molecules act as hubs, orchestrating numerous metabolic reactions. In healthy livers, these hub molecules respond rapidly to starvation, ensuring an efficient and timely metabolic response. However, in obese livers, this temporal order is disrupted, even though the structural integrity of the network appears unaltered.
The team led by Keigo Morita and Shinya Kuroda employed multiomic data collected from both healthy and leptin-deficient obese (ob/ob) mice under starvation conditions. By constructing a comprehensive metabolic network, they identified ATP and AMP as crucial regulators in healthy livers. These molecules not only coordinated metabolic processes but also ensured positive or negative coregulation among other molecules. In obese mice, however, neither ATP nor AMP responded adequately to starvation, leading to a breakdown in temporal coordination and coregulation.
This breakthrough underscores the significance of understanding both the structural and temporal dimensions of metabolic networks. The method developed by the researchers combines structural and temporal analyses, providing deeper insights into complex biological systems. It opens new avenues for studying other biological phenomena involving multiple "omes," such as the genome or microbiome.
Kuroda envisions extending this approach to explore broader metabolic processes, including food intake and disease progression. By describing the global landscape of adaptation to starvation, the study paves the way for future investigations into how metabolic networks respond to various physiological challenges. Ultimately, these findings could lead to innovative strategies for managing metabolic disorders associated with obesity.
