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Researchers reveal the health-promoting benefits of the metabolic protein AMPK

September 13, 2021

Researchers at the Salk Institute developed a new system that improves scientific understanding of a health-promoting metabolic protein known as AMPK.
Experimenting with model mice, the team created a system that allowed them to control where AMPK was activated in the body.
Citing study results, the researchers demonstrated that AMPK activation in liver tissue helped alleviate fatty liver disease and had a positive impact on the rest of the body.

A report released by researchers from the Salk Institute enables scientists to better understand the working of the beneficial cellular protein AMPK. The paper was published in Cell Reports in 2019. It was funded by grants from the National Institutes of Health, the Glenn Center for Aging Research, the Leona M. and Harry B. Helmsley Charitable Trust, the American Heart Association, the American Cancer Society, and Philippe Foundation Inc. AMP-activated protein kinase (AMPK) is a central metabolic regulator that balances nutrient supply and energy demand within cells. For instance, AMPK is activated throughout the body during caloric restriction or after exercise. It alters the activity of numerous other genes and proteins, helping keep cells alive and functional even when they are low on fuel. Studies in animals have linked AMPK activation to health-promoting effects. It’s been shown to improve cardiovascular health, reverse diabetes, alleviate mitochondrial disease and even improve lifespan. However, scientists have been unable to assess the specific impact of increasing AMPK without changing its activity throughout the life of an organism. The new system by Salk Institute researchers overcomes this barrier and lets scientists investigate where, when, and how AMPK carries out its therapeutic and molecular functions. Scientists at Salt engineered a special version of AMPK that allows them to control where it could be activated (in specific tissues or throughout the body). This way, they were able to activate AMPK in livers of adult mice with fatty liver disease. “This model will allow us to answer questions that scientists could not answer before. It really gives us a new way to define the health benefits of this specific enzyme in a wide variety of diseases,” said Professor Reuben Shaw, the senior study author and head of the Salk Cancer Center. To test the model, the team deliberately fed a subset of the research mice with a high-fat diet to induce obesity and excess accumulation of fat cells in the liver. This was equivalent to nonalcoholic fatty liver disease (NAFLD) in humans, the leading type of chronic liver disease among American adults. In both NAFLD and control mice, levels of liver fat dropped after AMPK was activated. Existing fats were broken down and new fat production slowed down. Moreover, mice that were fed with a high-fat diet appeared to gain protection from weight gain and obesity, and also had a lower incidence of liver inflammation. “This paper confirms that AMPK is a good target for treating NAFLD. It’s further confirmation that AMPK activators should be tested clinically,” said Daniel Garcia, the study’s first author and a senior research associate at Salk. In addition to the positive effects on liver fat, AMPK activation appeared to lower levels of fat elsewhere in the body. This implied that hormones discharged by the liver were affected as well. “These results indicate that AMPK could potentially be a powerful treatment to a host of diseases in humans,” added Dr. Shaw. The team is now looking to study the impact of AMPK activation in other tissues. They hope to establish whether AMPK activation in muscle tissue mimics exercise and whether activation later on in an organism’s life can improve lifespan.

References: https://www.salk.edu/news-release/salk-scientists-uncover-the-health-effects-of-metabolic-magic-bullet-protein

Researchers reveal the health-promoting benefits of the metabolic protein AMPK

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