Diabetic or obese patients suffering advanced heart failure have higher levels of fat embedded in their hearts and greater molecular evidence of haywire cardiac metabolism, a research team led by cardiologists at The University of Texas Medical School at Houston reports in the November issue of the FASEB Journal.
Heart failure, progressive and potentially fatal weakening of the heart muscle, is associated with both obesity and diabetes, but the mechanisms by which damage occurs are not well-understood, said senior author Heinrich Taegtmeyer, M.D., Ph.D., professor of cardiology.
"In cardiology, we've long been concerned about fat accumulating in the artery walls and blocking the flow of blood to the heart. What we are finding now is that the buildup of fat doesn't stop in the blood vessels, it's actually worse in heart muscle cells," Taegtmeyer said. "We also report in this paper that diabetes and obesity appear to cause metabolic irregularities in the heart tissue."
Gene expression and protein findings in the paper provide potential long-term targets for treating heart failure, which afflicts 5 million U.S. patients annually.
Researchers examined 27 failing hearts that were removed during transplants and compared them to eight donor hearts that were not failing but were otherwise unsuitable for transplant.
Eight of the failing hearts (30 percent) showed high levels of triglycerides – a fat storage and transport molecule. Levels of triglycerides in failing hearts were four times the level in obese or diabetic patients as they were in non-failing hearts.
The research team associated this buildup of triglycerides in the heart muscle, called lipotoxicity, with dysfunctional expression of genes related to the heart's metabolism of fatty acids, its contractile function, and an inflammatory protein known to contribute to insulin resistance.
The human results track with a rat model of the lipotoxic heart, which has been shown to cause improper cardiac contraction in the rodents, said first author Saumya Sharma, M.D., a cardiology fellow and researcher in Taegtmeyer's lab.