Mitochondria the culprit behind increased risk of heart failure in diabetics

Misshapen mitochondria could explain the two- to five-fold increased risk of heart failure in diabetics, according to research out of the University of Iowa.

Carver College of Medicine researchers, led by E. Dale Abel, MD, PhD, discovered through mouse models that excess fat in the heart—a commonality in obese and diabetic patients—can compromise heart cells’ ability to produce energy by directly distorting cells’ mitochondria.

“Diabetes, which affects almost 30 million Americans, 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,” Abel said in a release.

Mitochondria in healthy cardiomyocytes do use fatty acids as fuel, Abel explained, but can also utilize glucose, lactate and ketone bodies to create energy. If a heart is padded with too much excess fat, cells’ mitochondria will naturally overuse those adipose cells for energy production.

Abel’s team mimicked diabetes in genetically modified mice and used a novel 3D electron microscopic cellular imaging technique to observe the mitochondria in a lipid-overloaded environment.

The researchers found fatty acid uptake to the heart more than doubled in the rodent models, resulting in thin, twisted mitochondria that looked far from healthy organelles. Conventional electron microscopy would display the mitochondria as fragmented, the release explained, but up close, a mitochondrion looked “almost like a noodle snaking through the heart.”

These structural changes were a result of increased levels of reactive oxygen species (ROS), according to the research, which can alter the activity of proteins integral to mitochondria’s shape and size. By manually suppressing ROS, Abel et al. were able to restore the organelles’ healthy shapes, despite the sustaining lipid overload.

“We have demonstrated and detected how increasing the amount of fat that the heart consumes leads to dramatic changes in the structure and function of the mitochondria in the heart,” Abel said. “These studies provide a new window into how these changes to mitochondria could occur in the lipid-overloaded heart."

Abel and colleagues' research was published in Circulation Research late last year.