Source: University of Iowa
Summary: A new study has identified how excess fat in the heart, a common feature in diabetes and obesity, can harm the cells’ essential ability to produce energy.
The heart is the most energy craving organ in the body. Healthy heart cells (cardiomyocytes) consume fuel molecules to produce the energy to keep the heart pumping. This so-called energy production takes place inside the mitochondria, self-contained “powerhouse” organelles found in the cells. Although fatty acids are used as a primary fuel by the mitochondria, they can easily adapt to use other fuel molecules such as including glucose, lactate, and ketone bodies. However, diabetes reduces the heart muscle’s metabolic adaptability and causes heart cells to overuse fat as a metabolic fuel. Researchers from the University of Iowa in a new study has identified how excess fat in the heart, a common feature in diabetes and obesity, can harm the cells’ essential ability to produce energy. They believe the mechanism may contribute to the 2 to 5 – fold increased risk of heart failure in people with diabetes. The study findings were published in the journal Circulation Research.
The research team used genetically modified mice that mimic the increased fatty acid uptake (lipid overload) that characterizes diabetes to investigate the consequences of cardiac lipid overload on mitochondria. The lipid overload caused structural changes in the mitochondria that were observed when imaged by conventional electron microscopy. The study also revealed prolonged lipid overload leads to increased levels of damaging substances called reactive oxygen species (ROS). The excess ROS disrupts the mitochondrial network by altering the activity of several important proteins. The findings suggest that cardiac lipid overload disrupts normal mitochondrial structure, which may impair energy production and compromise heart function.
Prof. E. Dale Abel said, “We have demonstrated and detected how increasing the amount of fat (lipid) that the heart consumes leads to dramatic changes in the structure and function of the mitochondria in the heart. These studies provide a new window into how these changes to mitochondria could occur in the lipid-overloaded heart.”
More Information: Kensuke Tsushima et al, “Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission Novelty and Significance”, Circulation Research (2017). DOI: 10.1161/CIRCRESAHA.117.311307