Obesity-induced heart disease, which affects up to 10 per cent of the population in certain age ranges, is considered an untreatable condition. Seventy-five per cent of people don’t survive more than five years beyond diagnosis.
Researchers from the Metabolic Reprogramming Laboratory have found a link between obesity-induced heart disease and amyloid beta, a protein that has previously been implicated in the development of Alzheimer’s disease. The results of the study were recently published in Nature Communications.
Their data revealed that amyloid beta is secreted from fat tissue into the bloodstream and that obesity results in higher levels of amyloid beta in the blood. This led the researchers to ask whether amyloid beta was a causative factor in heart disease, so they treated normal lean mice with amyloid beta and then followed the heart metabolism and function of the mice.
It was found that amyloid beta did induce cardiac disease, just like obesity. It was discovered that amyloid beta accumulated in the mitochondria of the heart – the powerhouses of the cell that generate energy – and prevented energy generation in heart muscle cells. Because the heart uses so much energy to pump blood, this is sufficient to cause heart disease.
To the researcher’s knowledge, this is the first time that amyloid beta has been implicated in a disease that is not Alzheimer’s. To this point, it was thought that the negative effects of amyloid beta were restricted to the brain, where the protein is known to accumulate and cause the deposition of brain plaques that contribute to the development of Alzheimer’s Disease.
Results of this study are the first to describe the production and release of amyloid beta by fat tissue as a cause of heart disease. The discovery goes beyond explaining the causes, and has identified a possible approach to treat obesity-related heart failure.
There have been numerous therapies and drugs developed in recent years that have been very effective in blocking the effects of amyloid beta and have proved safe in humans, but most have failed to effectively treat Alzheimer’s disease for various reasons. However, this suggests that these therapies could be repurposed for cardiac disease.
When researchers from the Metabolic Reprogramming Laboratory treated obese mice with one of these developmental Alzheimer’s disease drugs, they confirmed that it did indeed prevent the progression of cardiac disease caused by obesity.
As these therapies already exist and have been safety tested in humans, it would be feasible to move directly to clinical trials in patients with heart disease. This will reduce the drug development process by around 10 years.
The researchers are now planning a proof-of-concept clinical study with colleagues at The University Hospital, Geelong, which is designed to test whether these Alzheimer’s disease therapies can improve heart function in patients with early heart failure.
