In patients with type 2 diabetes, the heart becomes starved of energy, leading to decreased recovery in the event of a heart attack. Diabetes is associated with high blood glucose and high blood lipids. Diabetes research tends to focus on the effects of high glucose, but changes in glucose concentrations do not explain why there is an energy deficit in the heart in type 2 diabetes.
It is known that the heart becomes laden with lipids in diabetes. Yet, there have been very few studies investigating the consequences of these high levels of lipids in the heart. Neither the specific lipids causing the metabolic upheaval that leads to energy starvation in the heart, nor the signalling pathways on which they are exerting these effects, have been identified.
New research from the Heather Group has interrogated whether the overload of lipids in the heart could be influencing the energy generation by the heart’s mitochondria. Researchers have 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. According to lead researcher Associate Professor Lisa Heather: “This has negative consequences for the diabetic heart during ischaemia, as this regulation allows the healthy heart to shut down wasteful ATP breakdown during ischaemia, but this preservation of precious ATP is lost in diabetes. This may contribute to why patients with diabetes do significantly worse during a heart attack.”
Consequently, the team have demonstrated the necessity of focusing research efforts on the high levels of lipids in the circulation that disrupt a large number of process in the heart. They also demonstrate that targeting this lipid overload is a valid therapeutic target for the diabetic heart. Prof Heather said: “The therapeutic challenge lies in finding the ‘Goldilocks zone’ - we need lipids to provide the energy to keep the heart beating, but it's when we have too much that we see the negative effects as in diabetes. Too much or too little fat is bad for the heart, so we need to find a therapeutic approach that gets it just right!”
The full paper “Diabetic mitochondria are resistant to palmitoyl CoA inhibition of respiration, which is detrimental during ischaemia” is available to read in The FASEB Journal.
The paper is also featured in the i Newspaper both online and in print: New discovery could help diabetics avoid lasting heart attack damage (inews.co.uk)