There needs to be just the right amount of fats in the heart for optimal function - not too much and not too little. In a new study from the Sanford-Burnham Prebys Medical Discovery Institute, scientists look at the accumulation of a particular type of fat, ceramides, in the heart.
Ceramides are a type of fat that provide both beneficial and harmful roles in the body. On the positive side, ceramides form cellular membranes and regulate cellular energy metabolism. In the skin, ceramides promote the barrier property of the epidermis, the outermost layer of the skin. But if someone eats too much fat or eats too many calories, heart disease can develop.
Accumulation of ceramides in the heart is tied to a type of heart disease called lipotoxic cardiomyopathy (LCM), which scientists believe to be primarily a result of diabetes and severe obesity. LCM develops when the heart transitions from taking energy from glucose oxidation to fatty acids like ceramides. Now, the study of ceramides has lead scientists to identify novel therapeutic targets to prevent LCM or at least reverse the effects of the disease.
Researchers began their study with a Drosophila model of LCM. Drosophila is a species of fruit fly commonly used in scientific studies. “Elevated levels of ceramide - driven by genetic or dietary manipulation - is sufficient to induce LCM," explained senior author Rolf Bodmer, PhD.
Bodmer’s study is the first to provide “direct evidence” of the link between ceramides and heart disease. However, it also supports other indirect evidence discovered in past studies. Scientists from the present study also successfully stopped LCM symptoms by inhibiting ceramide production.
Researchers started by manipulating ceramide levels in Drosophila hearts, either with diet or changes in genetic expression of genes that break down ceramides. Regardless of what method researchers used to increase ceramide levels, they saw similar, negative effects in the fruit flies. However, when researchers reduced ceramide levels excessively, the fruit flies experienced restrictive cardiomyopathy (RCM), a rare form of heart disease characterized by restrictive filling of the ventricles; in RCM, the contractile function of the heart and wall thicknesses are normal.
"Too much or too little ceramide is detrimental to heart function - the levels need to stay within a well-balanced range to ensure robust cardiac function,” Bodmer explained.
Researchers also tested several ceramide-interacting proteins (CIPs), which are influenced by ceramide, leading to apoptosis (programmed cell death), heart muscle protein instability, and deregulation of lipid metabolism.
"Identifying novel lipid/protein interactions is valuable because they represent possible new targets to treat lipotoxic cardiomyopathies or end-stage heart failure," explained first author Stanley Walls, PhD.
The present study signifies an important opportunity for medical professionals to control ceramide levels as part of a treatment approach for LCM. In the future, Bodmer and the other researchers want to expand their research to studying the role of ceramides in cancer development.
The present study was published in the journal Cell Reports.