by Jennifer Brown, Carver College of Medicine
Eating a ketogenic diet rescued mice from heart failure, according to a recent study led by University of Iowa Carver College of Medicine researchers.
The study, published online Oct. 26 ahead of the November issue of the journal Nature Metabolism, was one of three companion papers from independent research teams that all point to the damaging effects of excess sugar (glucose) and its breakdown products on the heart. The UI study also revealed the potential to mitigate that damage by supplying the heart with alternate fuel sources in the form of high-fat diets.
Given its need for a constant, reliable supply of energy, the heart is very flexible about the type of molecules it can burn for fuel. Most of the heart’s energy comes from metabolizing fatty acids, but heart cells can also burn glucose and lactate, and also ketones.
Too much glucose, however, has been linked to heart failure, and heart failure is a leading cause of death in people with Type 2 diabetes. Heart biopsies from people with heart failure show an accumulation of sugar molecules in the heart, suggesting that this “backup” of glucose, because it is incompletely metabolized, may be contributing to the damage. The new UI study investigated how glucose and accumulation of these metabolites contribute to heart failure.
The UI team, led by E. Dale Abel, MD, PhD, professor and chair of the Department of Internal Medicine, removed a critical protein from heart cells in mice. This protein, called the pyruvate carrier protein, is responsible for taking pyruvate, derived from glucose metabolism, into mitochondria where it's further metabolized to make energy. Levels of this protein are reduced in human failing hearts. Removing the pyruvate carrier protein prevents heart cells from using glucose as an energy source and causes a backup of the glucose-derived molecules, similar to what has been seen in human heart failure.