Research conducted on mice has revealed that obesity exhibits a specific response to periods of fasting.
Periodic or intermittent fasting has become a popular strategy for improving health and metabolism. It involves extended periods of calorie restriction followed by windows of normal eating.
However, the authors of a new study found that these efforts may be undermined by the cunning behavior of fat deposits. According to scientists from the University of Tokyo, the issue lies in a “hidden disruption of the liver’s ability to adapt to fasting.”
What Did the Scientists Discover?
The researchers observed changes in the livers of healthy mice as well as those with obesity, particularly during periods of food deprivation when leptin (a hormone that regulates appetite) was lacking.
While both groups of mice maintained a similar metabolic network—a system of molecules in the liver that work together to manage energy—they exhibited a significant difference in their response time to hunger.
“In a healthy liver, energy-related molecules like adenosine triphosphate (ATP) and adenosine monophosphate (AMP) respond quickly to fasting and regulate numerous metabolic reactions. However, this process is disrupted in obesity,” explained Shinya Kuroda, a professor of systems biology and the lead author of the study, to BBC Science Focus.
In other words, in healthy mice, energy-related molecules such as ATP and AMP acted as central hubs, swiftly orchestrating metabolic changes to conserve and redistribute energy. In contrast, in obese mice, these molecules were unresponsive to changes, leading to a sluggish and disorganized reaction to fasting.
When ATP and AMP respond quickly to food shortages, they help the liver switch from energy storage to energy burning. This shift is believed to provide many benefits of intermittent fasting, such as weight loss and improved blood sugar control.
By combining structural and temporal analyses of metabolism, the team discovered that obesity causes a sort of metabolic “jet lag,” disrupting timing rather than just the flow of key molecular processes.
“Our findings could potentially enhance the therapeutic effects of intermittent fasting. Next, we need to identify blood-based biomarkers that can be easily tracked in humans. Ultimately, clinical research is needed to confirm our results. It’s a long road ahead, but a journey of a thousand miles begins with a single step,” noted Professor Kuroda.
The study’s results were published in the journal Science Signaling.