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Research on mice shows that obesity changes how the body responds to 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.
But a new study suggests those efforts may be undermined by how fat tissue behaves. Researchers at the University of Tokyo say the problem is a “hidden disruption of the liver’s ability to adapt to fasting.”
What Did the Scientists Discover?
The team examined the livers of healthy and obese mice, focusing on fasting periods when levels of leptin — the hormone that regulates appetite — fall.
While both groups shared a similar metabolic network — a system of liver molecules that manage energy — they differed in how quickly that network responded to fasting.
“In a healthy liver, energy-carrying molecules such as adenosine triphosphate (ATP) and adenosine monophosphate (AMP) respond quickly to fasting and regulate many metabolic reactions. But that process is disrupted in obesity,” said Shinya Kuroda, professor of systems biology and the study’s lead author, to BBC Science Focus.
In healthy mice, ATP and AMP act as central hubs, swiftly orchestrating metabolic changes to conserve and redistribute energy. In obese mice, those molecules are unresponsive to changes, producing a sluggish and disorganized reaction to fasting.
When ATP and AMP respond quickly to food shortages, they help the liver switch from storing energy to burning it. That switch likely underlies many of intermittent fasting’s benefits, such as weight loss and improved blood sugar control.
By combining structural and temporal analyses of metabolism, the team found that obesity creates a kind of metabolic “jet lag,” disrupting timing more than the flow of key molecular processes.
“Our findings could help improve the therapeutic effects of intermittent fasting,” said Professor Kuroda. “Next, we need to identify blood-based biomarkers that can be tracked in people, and then conduct clinical research to confirm the results. It’s a long road, but this is a first step.”
The study’s results were published in the journal Science Signaling.
