Limiting the release of fat into the bloodstream during heart failure could help improve outcomes

Researchers at the University of Alberta have found that limiting the amount of fat that the body releases into the bloodstream from fat cells during heart failure can help improve outcomes for patients.

In a recent study published in American Journal of Physiology, Jason Dyck, professor of pediatrics at the School of Medicine and Dentistry and director of U’s A Cardiovascular Research Center, found that heart failure mice treated with a drug that blocks the release of fat into the bloodstream from fat cells saw less inflammation in the heart and body. and had better outcomes than the control group.

“Many people believe that, by definition, heart failure is just a condition of the heart. But it is much broader and is affected by multiple organs,” said Dyck, who is a Dr. Canada, chair of molecular medicine, is also a member of the Alberta Institute of Diabetes and the Institute for Women and Child Health Research. “What we’ve shown in mice is that if you can target fat cells with a drug and limit their ability to release stored fat during heart failure, you can protect the heart and improve heart function.”

“I think it really opens the door to other ways of investigating and treating heart failure,” Dyck remarked.

In times of stress, like heart failure, the body releases stress hormones, such as epinephrine and norepinephrine, to help the heart compensate. But because the heart can’t function better – and is actually further damaged by forcing it to pump faster – the body releases more stress hormones and the process cascades down, and heart function continues to decline. Therefore, beta-blockers designed to block the effects of stress hormones on the heart are common treatments for heart failure.

The release of stress hormones also triggers the release of fat from storage deposits in fat cells into the bloodstream to provide the body with extra energy, a process called lipolysis. Dyck’s team found that during heart failure, fat cells in mice also became inflamed throughout the body, mobilizing and releasing fat faster than normal and causing inflammation in the heart and the rest of the body. This inflammation put additional stress on the heart, adding a cascading effect, increasing the damage and reducing the work of the heart.

“Our research began by studying how the function of one organ can affect other organs, so I found it very fascinating to discover that fat cell can affect heart function in the case of heart failure,” Dyck said. “Fortunately, we had a drug that could inhibit the mobilization of fat from fat cells in mice, which actually protected the heart from damage caused by inflammation.”

Dyck points out that while his results are promising, more needs to be done to better understand the exact mechanisms at play in the process and to develop a drug that could work on humans.

“This work is evidence of a concept that shows that abnormal fat cell function contributes to worsening heart failure, and we are now working on understanding the mechanisms by which the drug works to better limit lipolysis,” he said. “Once we get that, it’s a launch pad to make sure it’s safe and effective, then upgrading to our chemists, and then maybe some early testing on humans.”

Dyck said the findings – and a better understanding of how organ functions affect other organs – could be used to develop new approaches to several other diseases.

“We know that people have a high rate of lipolysis when they have heart failure, so I guess this approach would benefit all types of heart failure,” he said. “But if you consider that inflammation is associated with a wide range of different diseases, such as cancer, diabetes or other forms of heart disease, then this approach could have a much broader benefit.”

Source:

Faculty of Medicine and Dentistry, University of Alberta

Journal reference:

Takahara, S., and others. (2021) Inhibition of ATGL in adipose tissue improves cardiac rearrangement induced by isoproterenol by reducing adipose tissue inflammation. American Journal of Physiology-Physiology of the Heart and Circulation. doi.org/10.1152/ajpheart.00737.2020.

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