The hungry heart
A normal healthy heart has the ability to choose its fuel from the menu of bioavailable substrates in the body. Glucose and fatty acids are the most common substrates, and the healthy heart switches seamlessly between the two depending on which is most available. For example, if you eat a candy bar, there is ample glucose in the blood, and the heart primarily uses that as its fuel source. In contrast, after going without food for some time, blood-sugar levels drop and the heart switches to fatty acids to provide its energy. The heart needs energy to contract, relax, repair, and rejuvenate itself.
Change in the heart’s shape, size, structure and pathology due to injury is called cardiac remodeling. A hallmark of an injured heart—whether it’s injured by diabetes, ischemia, hypertension, or heart failure—is that it becomes inflexible to switching fuels. Ketone bodies—an alternative fuel source—are present in blood at low levels in healthy conditions, but circulate at increased concentrations in heart failure, with the level of ketone bodies being directly proportional to the severity of the heart damage. The relationship between ketone-body metabolism (oxidation) and remodeling is an emerging area of research. The goal is to find biochemical interventions—either through diet or drug—that can promote the best fuel for the heart to recover from remodeling.
A new study by Peter A. Crawford, M.D., Ph.D., associate director in the Cardiovascular Pathobiology Program at Sanford Burnham, explores the role of ketone bodies as a fuel in normal and injured hearts. Using mice with hearts that lack the enzyme to metabolize ketones, Crawford’s research team systematically measured what happens in a heart that can’t metabolize ketones. Their findings show that high levels of circulating ketones do not induce abnormalities in these hearts, and that hearts become programmed to rely more heavily on fatty acids as a fuel under these conditions. Importantly, the research also showed that the inability to metabolize ketones predisposes the heart to worsened cardiac remodeling that occurs from injury.
“These are the first studies to examine what happens to the heart when it can’t metabolize ketones. Our next step is to perform targeted studies to quantify the oxidation of ketone bodies by the human remodeling heart to see if there is an optimal window of ketone metabolism that provides protection against remodeling,” said Crawford. “Eventually, we hope to help develop personalized nutritional and pharmacological therapies that protect the heart from injury, and help it recover. The ultimate goal is to mitigate the devastating personal and economic tolls of congestive heart failure.”
The study was published in Molecular Metabolism and at: http://www.molmetab.com/article/S2212-8778(14)00136-7/abstract