In a 2020 paper published in JCI Insight, the Heather lab found that during early onset diabetes, cardiac mitochondria work more slowly because mitochondrial proteins become hyperacetylated, decreasing the ability of the heart to use fuel for energy production. However, they demonstrated that a mitochondrial deacetylase SIRT3 activator, called honokiol, can reverse the hyperacetylation, and thus increase the amount of energy within the heart.
In a 2021 paper published in The FASEB Journal, the lab found that a specific fatty acid intermediate called Palmitoyl CoA, an 'activated' form of palmitic acid, can regulate the phosphorylation apparatus within the mitochondria, but this regulation is lost in the lipid-loaded environment within the diabetic heart. This finding demonstrated that targeting lipid overload in the diabetic heart is an important therapeutic target.
Later in 2021, in a paper published in Diabetes, Prof Heather's team, in collaboration with the Carr and Tyler groups, found that a drug known as molidustat could reduce the risk of heart failure for people with diabetes who have heart attacks.
The Heather Group has challenged the traditional view of lipids as simply sources of energy and membrane structures, and opened up a new area of research into lipids as distinct signalling molecules regulating the diabetic myocardium. Prof Heather's research has shown that lipids can regulate post-translational modifications, transcription factor activation and inhibit transporter proteins.
Prof Lisa Heather has now been awarded a two year extension to her Fellowship, which will allow her to generate preliminary data for a future Senior Fellowship application.
Prof Heather said: "Going forward we will take a hypothesis-generating approach to understand the scale of this metabolic regulation in diabetes. Using a combination of novel chemical metabolite probes and metabo-genetic approaches, we will profile the cellular consequences of disrupted metabolism. We hope this will fundamentally change how we understand the hyperlipidaemia and metabolic dysfunction that occurs early on in the development of diabetic heart disease."