Scientists discover how to prevent high-fat diets from wrecking your metabolism

IRVINE, Calif. — It’s no secret that high-fat diets can throw off metabolism, increasing risks for disease. However, the underlying reasons are a lot less clear. Biologists from the University of California-Irvine have now made a key discovery about how to prevent harm if your diet features too much fatty food.

The researchers narrowed their focus to a protein complex called AMPK, which acts as a cellular energy sensor, capable of sensing the body’s nutrition in order to maintain a proper balance. For instance, if AMPK detects that glucose is low, it can signal the body to use fats as energy instead.

However, consuming fat blocks the activity of this complex, which is what drives metabolism out of whack. Unfortunately, researchers say studies haven’t investigated how that exactly happens, especially among living organisms. In this study, the team took a protein called SAPS3 — which appears to have a close connection to AMPK and its mechanisms — and removed it from the mice genome. They then fed mice a diet composed of 45 percent fat.

The team wasn’t expecting to find what they did.

“Removing the SAPS3-inhibiting component freed the AMPK in these mice to activate, allowing them to maintain a normal energy balance despite eating a large amount of fat,” says Mei Kong, professor of molecular biology & biochemistry and the study’s corresponding author, in a university release. “We were surprised by how well they maintained normal weight, avoiding obesity and development of diabetes.”

diabetes
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Inhibiting SAPS3 could be a new way to address metabolic disorders

“If we block this inhibition activity, we could help people reactivate their AMPK,” says first author Ying Yang, a project scientist in the Kong lab. “It could help in overcoming disorders such as obesity, diabetes, fatty liver disease and others. It’s important to recognize how important normal metabolic function is for every aspect of the body.”

This could be groundbreaking, particularly considering the prevalence of obesity around the world. In fact, estimates project that over half of the world will be overweight or obese by 2035, compared to 38 percent in 2020, according to the World Obesity Federation.

According to the National Center for Biotechnology Information, the number of people with diabetes will rise to 578 million by 2030, which would be a 25-percent increase from 2019. The team is already developing molecules that could inhibit SAPS3 and restore metabolism. They look ahead to studying the role of SAPS3 in other conditions with disrupted metabolism as well, like cancer and aging.

The findings are published in the journal Nature Communications.

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