June 22, 2024
University of Oklahoma Researchers Uncover Complex Interplay Between Liver Fat and Insulin Sensitivity: MLN4924's Role in Preventing Fatty Liver Disease

University of Oklahoma Researchers Uncover Complex Interplay Between Liver Fat and Insulin Sensitivity: MLN4924’s Role in Preventing Fatty Liver Disease

New research from the University of Oklahoma (OU) sheds light on the intricate relationship between liver fat accumulation and insulin sensitivity. The study, published in The Proceedings of the National Academy of Sciences, builds on previous findings by Tiangang Li, Ph.D., and his team at OU Health Harold Hamm Diabetes Center.

In their earlier work, the researchers discovered that MLN4924, a drug initially developed to suppress cancerous tumors, could enhance insulin sensitivity and lower blood glucose levels. The drug functions by obstructing the degradation of a protein essential for cells to respond to insulin.

In the latest study, the team eliminated a gene in the liver called Cul 3. When Cul 3 is present, MLN4924 inhibits it to prevent the protein’s degradation. By removing the gene, the researchers gained a deeper understanding of the consequences when mice consume a high-fat diet.

The absence of Cul 3 in the mice prevented liver fat accumulation, even in obese animals. However, this fat-free liver came at a cost: the fat was redirected to other tissues like muscle, where it shouldn’t be stored. Consequently, the muscle, the body’s largest organ, exhibited a diminished response to insulin, leading to high blood sugar levels.

Li explained, “By eliminating the gene, we successfully prevented fat accumulation in the liver, but this actually worsened insulin resistance in the muscle. This discovery underscores the interconnectedness of fat metabolism in these organs.”

These findings underscore the importance of not only reducing liver fat but also addressing obesity and improving insulin sensitivity for effective treatment of fatty liver disease. This is crucial as the fat that enters the liver can also accumulate in other tissues, exacerbating health issues.

*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it