A research team at Baylor College of Medicine and collaborating institutions investigated the function of the protein Rev-erbα/β, a key component of the circadian clock, and found that its absence could lead to “heart disease development in animal models and human patients.”
The team reports in the journal Circulation that Rev-erbα/β in cardiomyocytes mediates a normal metabolic rhythm that enables the cells to prefer lipids as a source of energy during resting time. Removing Rev-erbα/β disrupts this rhythm, reduces the cardiomyocytes' ability to use lipids in the resting time and leads to progressive dilated cardiomyopathy and lethal heart failure.
"We studied how the Rev-erbα/β gene influenced the metabolism of the heart by knocking it out specifically in mouse cardiomyocytes. Lacking the gene resulted in progressive heart damage that led to heart failure,” says co-corresponding author Dr. Zheng Sun, associate professor of medicine, section of endocrinology, diabetes and metabolism and of molecular and cellular biology at Baylor.
To learn how Rev-erbα/β mediated its effects, the team analyzed gene and protein expression and a comprehensive panel of metabolites and lipids. They found that the Rev-erbα/β gene is highly expressed only during the sleep hours, and its activity is associated with fat and sugar metabolisms.
"The heart responds differently to different sources of energy, depending on the time of the day. In the resting phase, which for humans is at night and for mice in the day, the heart uses fatty acids that are released from fats as the main source of energy. In the active phase, which is during the day for people and at night for mice, the heart has some resistance to dietary carbohydrates. We found that without Rev-erbα/β, hearts have metabolic defects that limit the use of fatty acids when resting, and there is overuse of sugar in the active phase," Sun explains.
"We suspected that when Rev-erbα/β knockout hearts cannot burn fatty acids efficiently in the resting phase, then they don't have enough energy to beat,” he concludes.