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Biologists discover removing a protein inhibitor restores metabolic balance.
UC Irvine biologists found that removing the SAPS3 component in mice allowed them to maintain a normal energy balance despite consuming a high-fat diet. This discovery could lead to treatments for obesity, diabetes, and other metabolic disorders by targeting SAPS3 inhibition.
Eating lots of fats increases the risk of metabolic disorders, but the mechanisms behind the problem have not been well understood. Now, University of California, Irvine (UCI) biologists have made a key finding about how to ward off harmful effects caused by a high-fat diet. Their study was published recently in the scientific journal
“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.
Support for the project was provided by the National Institutes of Health and the American Cancer Society.