Biologists are discovering how to counteract the effects of a high-fat diet

UC Irvine biologists discovered that by eliminating the SAPS3 component of the AMPK protein complex, mice were able to maintain a normal energy balance even when eating a high-fat diet. This discovery, published in Nature Communications, reveals the possibility of developing SAPS3-inhibiting molecules to help restore metabolic homeostasis and combat metabolic disorders such as obesity, diabetes, and fatty liver disease. As metabolic-related diseases continue to rise globally, this research could lead to new approaches in treating these conditions.

Biologists have discovered that removing protein inhibitors restores metabolic balance.

Biologists at the University of California, Irvine, found that removing the SAPS3 component in mice allowed them to maintain a normal energy balance despite a high-fat diet. This discovery could lead to treatments for obesity, diabetes, and other metabolic disorders by targeting SAPS3 inhibition.

Eating too much fat increases the risk of metabolic disorders, but the mechanisms behind the problem are not well understood. Now, biologists at the University of California, Irvine (UCI) have made a major discovery about how to ward off the harmful effects of a high-fat diet. Their study was recently published in the scientific journal

Mei Kong

Mei Kong is a professor of molecular biology & biochemistry and the study’s corresponding author. Credit: UCI School of Biological Sciences

“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,” said Mei Kong, professor of molecular biology & biochemistry and the study’s corresponding author. “We were surprised by how well they maintained normal weight, avoiding obesity and development of diabetes.”

The discovery could eventually lead to a new way to approach metabolism-related conditions. “If we block this inhibition activity, we could help people reactivate their AMPK,” said 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.”

The researchers are working on developing molecules that could inhibit SAPS3 and restore the metabolism’s balance. They plan to next study SAPS3’s role in other conditions with disturbed metabolic systems, such as cancer and aging.

The discovery comes as metabolic-related diseases such as obesity and diabetes continue to rise. More than half of the global population is expected to be overweight or obese by 2035, compared to 38 percent in 2020, according to the World Obesity Federation. The number of people worldwide with diabetes is expected to rise to 578 million by 2030, up 25 percent from 2019, reports the National Center for Biotechnology Information.

Reference: “SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice” by Ying Yang, Michael A. Reid, Eric A. Hanse, Haiqing Li, Yuanding Li, Bryan I. Ruiz, Qi Fan and Mei Kong, 13 March 2023, Nature Communications.
DOI: 10.1038/s41467-023-36809-1

Support for the project was provided by the National Institutes of Health and the American Cancer Society.

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