Cardiac Knockout Mice Show Role of  Gene in Fat Metabolism

Scientists know that the heart predominantly uses lipids as fuel in order to function. However, recent research conducted by molecular biologist Dr. Weiqin Chen of Augusta University seems to reveal that both too many and too few of the lipid droplets required for normal heart function can lead to heart failure.

Chen is currently studying a regulator gene and a protein that could be the key to discovering how doctors could intervene in these types of heart maladies.

BSCL2 and ATGL – Regulating Heart Metabolism

Experts know that BSCL2 has been identified as a regulator gene for fat metabolism which determines the amount of white, beige and brown fat that the body produces. However, according to Chen’s laboratory tests, the gene also regulates ATGL, a protein that determines how much lipid the heart needs to burn for adequate energy.

The important research conducted by Chen has revealed a link between BSCL2 mutations and Berardinelli-Seip congenital lipodystrophy, a rare disease that causes patients to be completely unable to retain normal fat deposits. Complications lead patients to build up excess triglycerides, increased insulin-resistance and a greater risk of heart failure.

Both laboratory mice with the gene removed and individuals with the disease display similar symptoms. Chen has also discovered that these subjects no longer had the normal fat deposits in the heart that are required for regular heart function. She hints that the gene might also be important in maintaining the homeostasis of lipid accumulation essential to cardiac function.

Causes of Heart Failure

In research conducted on mice, Chen has discovered that, while the hearts of mice without the gene become larger and more active in burning fat, they lack the ability to store lipids effectively and eventually burn themselves out. This process increases in the knockout mice as a result of the increase of ATGL expression which frees up lipids from areas of the body where BSCL2 is knocked out. The heart eventually lacks sufficient energy to sustain itself, and the lipids circulating in the bloodstream simply can’t provide it with enough energy.

Both impaired BSCL2 and ATGL can have the same effect. Without enough ATGL, heart cells collect too much lipids, which can also lead to heart failure.

For a short time, the heart begins to use up glucose – similarly to fetal hearts – as it attempts to compensate for the inadequate lipid provisions. However, this change can only supply 30% of the required energy. As a result, the sugar is unable to sustain heart function for long and only acts as a temporary fix.

Ongoing Research

Having received a $2 million grant from the National Institutes of Health, Dr. Chen continues to study the specific effects of the impaired BSCL2 gene on normal heart function. BSCL2 gene knockouts have been linked most closely to severe heart dysfunction, and Chen’s practical research also supports her theory of a relevant link to the ATGL protein.

The ongoing studies and research conducted by Chen and her team now aim to shed further light on the impact of improper lipid burning in obesity and diabetes, while closely studying how lipid burning is regulated in the heart and how gene impairment can lead to heart failure. An emphasis on balance is also made, as ongoing scientific research shows that even problems like chronic stress can negatively impact the balance between BSCL2 and ATGL over time.