Investigating molecular mechanism of medium chain fats in muscle health and cardiovascular disease treatment

About the Project

Ketogenic diets, involving restricted carbohydrate and high fat consumption, have been proposed to increase skeletal muscle strength, with likely impacts on professional sports performance. In addition, these diets may provide a potential avenue for the treatment of skeletal muscle loss in old age (sarcopenia). Mechanisms for these effects are widely considered to be through the generation of small metabolic products produced by fatty acid breakdown, called ‘ketones’, that provide energy. However recent discoveries have identified roles for specific medium chain fatty acids, often used in these diets, that do not rely on ketone generation^1,2,3, but likely function through a range of mechanisms including the metabolic reprogramming of energy metabolism. These medium chain fatty acids have been demonstrated to increase muscle mass and grip strength in a clinical trial of middle aged and elderly^4,5. This suggested mechanism improving muscle health through dietary intake of medium chain fatty acids, in both sports and in healthy ageing.

Another importance area of muscle in health related to the heart, where coronary heart disease (CHD) provides 31% of global mortality worldwide. In England, in 2023 just over 3% of the population (1,862,500) had a diagnosis of CHD, and this is higher in Scotland (per capita 730,000). In total, in the UK 48,700 people under 75 died of cardiovascular disease in 2023. Surprisingly, a recent population-based cross-sectional study identified that with each 1g/day of a specific medium chain fatty acid (decanoic acid) consumed, the likelihood CHD decreases by 21%. Further evidence for a beneficial role for a specific medium chain fatty acid in CHD is through a rare mutation in a gene encoding an enzyme in fatty acid metabolism, where the mutation blocks the use of triglycerides in the heart, leading to fat build up, muscle loss and refractory heart disease. Surprisingly, dietary decanoic acid provide effective treatment in these patients. Thus, there is significant evidence for clinical impact of decanoic acid on cardiovascular disease, without a clear understanding of mechanism nor a direct evidentiary link to blends.

Our research has contributed to the development of a novel blend of medium chain fatty acids, called ‘K.vita’, through the discovery of molecular mechanisms associated with these fats beyond ketones^1,3 through the investigation of molecular mechanism the fatty acid components and efficacy. Our recent studies have also highlighted metabolic mechanisms of these fats including increasing mitochondrial load².

This project will investigate mechanisms underlying the effect of medium chain fatty acids in muscle health. This will include (i) enhancing muscle health at a cellular and molecular level, (ii) protecting muscle health during ageing; and (iii) in promoting cardiovascular health as one of the most common causes of mortality worldwide. The study with combine advance molecular cell biology and biochemical approaches, and include omics approached, in a range of cellular model. The project further includes advanced data analysis. As this project is likely to very competitive, those with Master degree qualification are particularly encouraged to apply.

References

1. Chang et al (2016) 139:431-443.
2. Pain et al (2024) Proc Natl Acad Sci U S A. 121:e2321874121.
3. Augustin et al (2018) Lancet Neurol. 17:84-93.
4. Kojima et al (2023) Nutrients, 15.
5. Ezaki & Abe (2023) Front Nutr 10:1284497