Failing Hearts Switch Fuels to Continue Generating Energy

A new study provides fresh biochemical insight into heart failure and may eventually lead to new diagnostic and pathology tests as well as therapeutic targets to prevent or slow progression of the disease. The findings suggest a new approach to help treat early stages.

The research was led by Daniel Kelly, MD, scientific director of the Lake Nona campus of Sanford Burnham Prebys Medical Discovery Institute (SPB; La Jolla, CA & Lake Nona, FA, USA) as a collaborative study by scientists from SPB, Duke University, University of Illinois, and University of Cologne.

“Our research shows that as the heart fails, it loses its ability to burn fatty acids—the building blocks of fat—and instead starts using ketone bodies as an alternative fuel. It’s almost like the heart is starving because it doesn’t have the enzymatic machinery to burn fat anymore,” said Dr. Kelly.

To better understand what metabolic changes occur in place of fatty acid-burning, the team studied well established mouse models of the early and late stages of heart failure. They analyzed heart muscle cells to identify enzymes involved in metabolizing fuel that may ultimately become targets for therapies. They found that levels of BDH1, an enzyme involved in ketone metabolism, were 2x as high in mice with both early stage and complete heart failure compared to normal animals.

“It was surprising that BDH1 was increased in the failing heart, because this is an enzyme that is involved in burning ketones,” said Dr. Kelly, “We find it more in brain and liver, but one wouldn’t expect it to be very active in the heart.”

The new results suggest that a heart in the midst of failure has the ability to reprogram itself to take in more ketones and use them in a lower oxygen consumption fuel metabolism than fatty acid metabolism. Future studies on whether this is a productive or a faulty adaptive fuel shift could lead to new therapeutic avenues. Improved treatments would also be good news as the prevalence of heart failure is expected to increase in the coming years.

The study was published January 27, 2016, in the journal Circulation.

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Sanford Burnham Prebys Medical Discovery Institute