For many years, scientists believed that helping the heart burn more fat for energy was generally a good thing. After all, fat is the heart’s main fuel source under normal conditions.
Every day, the heart beats more than 100,000 times and needs a huge amount of energy to keep blood moving throughout the body. Most of that energy comes from a process called fatty acid oxidation, in which heart cells break down fats to produce fuel.
However, a new study from UT Southwestern Medical Center suggests that there can be too much of a good thing. Researchers have discovered that when heart cells burn fat without the normal biological
controls that keep the process balanced, the result can be serious damage to the heart. Their findings provide new insights into how heart failure develops and may help scientists identify people at risk earlier in the disease process.
The study was published in the Journal of Clinical Investigation and was led by Dr. Jay Horton and colleagues at UT Southwestern.
Heart failure is a major health problem worldwide. It occurs when the heart becomes too weak or stiff to pump blood efficiently. Millions of people live with heart failure, and the condition is particularly common among older adults and people with obesity, type 2 diabetes, or metabolic syndrome.
Scientists have long observed an interesting change in the hearts of people with heart failure. Healthy hearts mainly rely on fat for fuel, but failing hearts often switch to using more glucose, a type of sugar. Researchers have debated for decades whether this shift is harmful or whether it is actually the body’s attempt to protect the heart.
The new study provides evidence that, under certain circumstances, reducing fat burning may actually help protect heart cells.
To investigate this question, the researchers used genetically modified mice. They removed two enzymes known as acetyl-CoA carboxylase 1 and acetyl-CoA carboxylase 2 from heart muscle cells. These enzymes normally act like traffic controllers, helping regulate how many fatty acids enter structures called mitochondria.
Mitochondria are often described as the power plants of cells because they generate most of the energy cells need to function. In heart cells, mitochondria are especially important because the heart requires a constant supply of energy.
Without the enzymes that regulate fat metabolism, fatty acids flooded into the mitochondria and were burned at unusually high rates. At first glance, this might seem beneficial because more fuel was being used. However, the researchers found that the excessive fat burning created a serious problem.
The uncontrolled process gradually depleted linoleic acid, an important fatty acid obtained from the diet. Linoleic acid plays a critical role in maintaining cardiolipin, a special lipid found inside mitochondrial membranes.
Cardiolipin is essential for keeping mitochondria healthy and functioning properly. It helps maintain the structure of the mitochondrial membrane and supports the machinery that produces energy.
As cardiolipin levels fell, the mitochondria began to malfunction. Their ability to generate energy declined, and the structure of the mitochondria became damaged. Eventually, the mice developed enlarged hearts and weakened pumping ability, a condition known as dilated cardiomyopathy, which is a common form of heart failure.
The researchers then explored whether they could prevent this damage. They tested drugs that block CPT1, a protein that helps transport fatty acids into mitochondria. When these drugs were given early, before significant heart damage had developed, they successfully prevented heart failure in the mice.
However, timing proved crucial. Once heart failure was already established, the treatment no longer improved heart function. This finding suggests that therapies aimed at heart metabolism may be most useful during the early stages of disease rather than after extensive damage has occurred.
The study also highlights cardiolipin as a potentially important marker of heart health. Monitoring changes in cardiolipin levels may one day help doctors identify patients at risk before symptoms become severe.
The research builds on earlier work from the same laboratory showing that blocking acetyl-CoA carboxylase enzymes can reduce fat accumulation in the liver. Interestingly, the new study demonstrates that changing fat metabolism can have very different effects in different organs. What may be beneficial in one tissue may be harmful in another.
In reviewing the findings, this study provides an important reminder that the body’s energy systems depend on balance rather than extremes. The results challenge the simple idea that more fat burning is always better for the heart.
Instead, the heart appears to require metabolic flexibility, allowing it to switch between fuels while maintaining healthy mitochondria. The study was performed in mice, so more research is needed to determine whether the same mechanism occurs in humans.
Nevertheless, the biological explanation is strong and may help guide future treatments for heart failure, particularly in people with obesity, type 2 diabetes, and metabolic syndrome. The findings offer a promising new direction for understanding how disrupted energy metabolism contributes to heart disease.
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The study was published in the Journal of Clinical Investigation.
Source: UT Southwestern Medical Center.
