Diabetes And Heart Disease Link: Overuse Of Fat For Fuel

The production of energy that fuels the pumping of our heart occurs inside mitochondria, the “power plant” organelles within our cells.

In healthy hearts, fatty acids are a mitochondria’s main source of fuel, though glucose, lactate, and ketone bodies are also used as needed. However, this adaptability to different fuel types is reduced when people have diabetes, causing heart cells to over-rely on fat for energy.

University of Iowa (UI) researchers discovered that an over-reliance on lipids (fat) for fuel leads to mitochondria that are small, misshapen, and inefficient energy producers. This may account for the two to five-fold increased risk of heart failure in people with diabetes.

“Diabetes…significantly increases the risk of heart failure, and one of the cardinal manifestations of the hearts of people with diabetes is the tendency to overuse fat as a metabolic fuel, which ultimately leads to mitochondrial and cardiac damage,” said study head E. Dale Abel, M.D., Ph.D., UI Carver College of Medicine. “These studies provide a new window into how these changes to mitochondria could occur in the lipid-overloaded heart.”

Using genetically modified mice with elevated heart lipids, the research team employed a 3D electron microscope to directly view structural changes in the fat-overloaded mitochondria. They noticed the organelles were thinner, and more twisted than mitochondria in healthy heart cells.

The study also showed these changes occurred because a lipid overload, overtime, triggers increased levels of reactive oxygen species (ROS). The ROS are harmful substances that alter the activity of several proteins responsible for mitochondria shape and size. Removing the excess ROS restored the presence of normal looking, efficient mitochondria.

The findings, published in Circulation Research, imply that a lipid overload in heart cells disrupts the normal structure of mitochondria, impairs their energy producing function, and may lead to cardiac damage.

Source: UI Carver College of Medicine
Photo credit: UI Carver College of Medicine

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