As if clogged arteries weren’t bad enough, the mere presence of fat in the heart may kill cells and eventually lead to heart failure, researchers suggest in the April 2001 Journal of Clinical Investigation.
Jean E. Schaffer and her colleagues at the Washington University School of Medicine in St. Louis believe that a surplus of long-chain fatty acids, the lipid molecules that the heart normally uses for fuel, may endanger cells if the fat accumulates beyond normal amounts. The buildup may prompt the organ’s cells to commit suicide.
Heart disease and the accumulation of fat in the organ often go hand in hand. This can be true whether the condition originates with an inherited defect, is associated with a disease such a diabetes, or “comes out of the blue,” as it might after a viral infection, says Schaffer.
She and her colleagues investigated the idea that heart disease may begin with a mismatch between the amount of fat entering the heart and the amount actually burned by the organ for energy. “Our work suggests that lipid accumulation alone is sufficient to cause cardiac dysfunction, ” she says.
As a diseased heart loses function, for unknown reasons the organ switches from metabolizing fatty acids to burning the simple sugar glucose for energy. “We don’t understand if [the switch] is initially helpful or it just happens,” says Schaffer. Whatever the case, she points out, the metabolic shift is permanent and eventually makes the situation worse.
The investigators genetically engineered mice that overproduce a protein for transporting fatty acids into the heart. The lipids accumulated in the muscle, and the fatty mouse hearts enlarged. Each mouse’s left ventricle, one of the heart’s two pumping chambers, lost nearly all its ability to pump blood. Premature death from heart failure soon followed.
The researchers’ tests tracking the fate of certain molecules in heart cells suggest that the lipids initiate an automatic program of cell death in the heart.
Exactly why lipids would set off this kind of mass cellular suicide is hard to know, says Schaffer. “Presumably, [the body] wants to get rid of cells that are accumulating a lot of lipids,” but this is pure speculation, says Schaffer. “Really, the next thing to understand is how to go from lipid accumulation to cell death.”
If the same processes cause human heart failure, the work has clear clinical implications, Schaffer contends. “We may be able to prevent diabetic [heart failure] by more rigorously controlling lipid levels” in diabetic patients’ blood, she says.