Prize motivation:
Myriam Aouadi at Karolinska Institutet is the recipient of the Leif C. Groop award for outstanding diabetes research 2022 for her major contributions in the field of targeted gene silencing and immunometabolism. Myriam Aouadi’s work has widened the understanding of macrophage heterogeneity, obesity-related inflammation and paved the way for the use of molecular approaches in finding new treatments for obese patients with type 2 diabetes and liver disease.
“I think this is a great recognition for the work that I am carrying out together with my research team. In our research, we strive to understand the role of the immune system in liver disease in obese patients with prediabetes and type 2 diabetes. An important goal is to contribute to the development of new treatments,” says Myriam Aoadi, principal investigator and associate professor at the Centre for Infectious Medicine at Karolinska Institutet.
Important cell type
Her research group is exploring the role of a cell of the immune system called macrophages in the development of nonalcoholic fatty liver disease. Macrophages are an important cell type in the immune system that defend the body against infectious diseases. These immune cells are found in all organs of the body, including the liver.
“We know that obesity is a risk factor for type 2 diabetes, and many patients with type 2 diabetes will also develop nonalcoholic fatty liver disease. The only available treatment today is liver transplantation. We believe that it is important to better understand the role of macrophages to be able to develop new treatment possibilities of the disease, which may lead to liver failure or liver cancer,” says Myriam Aouadi.
Increased knowledge
In 2019, Myriam Aouadi published a study in Nature Metabolism which increased the knowledge of the role of the liver macrophages in the context of nonalcoholic fatty liver disease. The researchers wanted to explore the molecular mechanisms driving the inflammatory activation of liver macrophages during obesity. The theory was that these cells contribute to the development of metabolic diseases by increasing inflammation, but their study showed something quite different.
“We discovered that macrophages in the liver were not becoming inflammatory during nonalcoholic fatty liver disease. Our results contradicted the original theory that liver macrophages could impact liver function by becoming inflammatory, which was unexpected. The study demonstrated that rather than attempting to develop anti-inflammatory drugs to treat nonalcoholic fatty liver disease other strategies should be explored,” says Myriam Aouadi.
Instead, the team found that liver macrophages contribute to oxidative stress in patients with nonalcoholic fatty liver disease. Oxidative stress occurs when there is an imbalance between harmful free radicals and antioxidants that help protect cells from damage.
Restored response
In their recent studies, Myriam Aouadi and her team showed that the liver produces a microRNA that blocks a protein that controls the antioxidative defense during nonalcoholic fatty liver disease. This microRNA, called miR144, is produced in high levels in the livers of obese individuals with oxidative stress
By using a technology that enables silencing of specific genes in liver macrophages, they were able to suppress the expression of miR144 in the immune cells, which led to decreased levels of free radicals in the liver and a restored antioxidant response.
”We hope that we will be able to develop new treatments for nonalcoholic fatty liver disease and other serious liver diseases by targeting macrophages and for example increasing the antioxidative response. This of great importance as the prevalence of type 2 diabetes is increasing and leads to nonalcoholic fatty liver disease in many cases,” says Myriam Aouadi.
The Leif C. Groop award of 100 000 SEK will be given to Myriam Aouadi during the annual Diabetes research day the 9th of February, arranged by Lund University Diabetes Centre (LUDC).
