Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PL08

Poster Communications

Cardiac metabolism in disease: All fuels are equal, but some fuels are more equal than others

L. Heather1

1. University of Oxford, Oxford, United Kingdom.

The heart requires more energy than any other organ in the body, to support its continual contractile activity. The vast majority of ATP is generated by mitochondrial oxidative phosphorylation, with small amounts obtained from anaerobic glycolysis. A number of fuels can be utilised by the heart to make ATP, including carbohydrates, fatty acids, amino acids and ketone bodies. Because different chemical reactions are needed to breakdown these independent fuels, this results in distinct substrates producing different amounts of ATP, and different amounts of oxygen being used to extract the energy. Thus, all fuels are equal in that they can all give you energy, but there are differences in the energetic benefits obtained and the associated costs involved. The healthy heart obtains 60-70% of its ATP from the oxidation of long chain fatty acids, with the remainder made predominantly from carbohydrates. Being able to change between these fuels is referred to as "metabolic flexibility", and is essential to match metabolism to the physiological conditions to which the heart is exposed, ensuring the best fuel is utilised in that environment. This can be regulated acutely, for example by allosteric mechanisms via the Randle cycle, or chronically, for example by transcription factors. In diseases such as heart failure and type 2 diabetes, cardiac metabolism becomes abnormal, which has consequences for energetics, metabolic flexibility and contractile function. Understanding the underlying mechanisms behind metabolic dysfunction in these diseases can help shed light on whether targeting cardiac metabolism has the potential for therapeutic benefit.

Where applicable, experiments conform with Society ethical requirements