A high-fat diet can indeed disrupt metabolism, but there are ways to mitigate its effects. A study published in the journal “Cell Metabolism” in 2021 showed that supplementing the diet with a specific type of fatty acid called n-3 polyunsaturated fatty acids (n-3 PUFAs) could prevent metabolic dysfunction caused by high-fat diets.
Eating a lot of fat raises the risk of metabolic disorders, but the mechanisms underlying the problem are unknown. Now, biologists at the University of California, Irvine have made an important discovery about how to avoid the negative effects of a high-fat diet. Their findings were published in Nature Communications.
The UC Irvine study focused on AMPK, a protein complex that senses the body’s nutrition and takes action to keep it balanced. If AMPK detects that glucose levels are low, it can increase lipid breakdown to produce energy in its place. Scientists have known for a long time that eating a lot of fat inhibits AMPK activity, causing the metabolism to become out of balance. However, until now, how cells block this mechanism has not been widely examined, especially in live models.
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. We were surprised by how well they maintained their normal weight, avoiding obesity and the development of diabetes.
Mei Kong
The UCI biologists decided to investigate, believing an AMPK component called SAPS3 serves a significant role. They eliminated SAPS3 from the genome of a group of mice and fed them meals with a 45 percent fat content. The results were startling even to the research team.
In the study, mice were fed a high-fat diet with or without n-3 PUFAs for eight weeks. The mice that received the n-3 PUFAs had improved glucose tolerance and insulin sensitivity compared to those that did not receive the supplement. Additionally, they had reduced inflammation in their adipose tissue and improved lipid metabolism.
Study shows how to prevent a high-fat diet from throwing metabolism out of whack
“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 and biochemistry and the study’s corresponding author. “We were surprised by how well they maintained their normal weight, avoiding obesity and the development of diabetes.”
The discovery could eventually lead to a new approach to metabolic 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 may aid in the treatment of disorders such as obesity, diabetes, fatty liver disease, and others.” It is critical to recognize the importance of normal metabolic function in all aspects 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 researchers believe that the n-3 PUFAs help prevent metabolic dysfunction by modulating the composition and function of gut microbiota, which plays a crucial role in regulating metabolism. These findings suggest that incorporating foods rich in n-3 PUFAs, such as fatty fish, flaxseed, and walnuts, into a high-fat diet could help prevent metabolic dysfunction.
