A mathematical model describing skeletal muscle fuel utilisation in humans

The 2007 European Study Group with Industry (ESGI) helped Unilever develop a mathematical model that describes skeletal muscle fuel utilisation in humans. This was motivated by an interest in how skeletal muscle switches from utilisation of lipids for fuel in the fasting state to use of glucose in the fed state, and how this metabolic switching varies depending on an individuals insulin sensitivity.

The work of the 59th ESGI has provided the basis for a cross-faculty PhD project – a BBSRC Industrial CASE Award - at Nottingham University under the supervision of Prof John King (Applied Mathematics) and Prof Ian McDonald (Centre for Integrated Systems Biology and Medicine). At the Study Group the major features of the project were elaborated.

"Critically the Study Group also offered an opportunity to familiarise both mathematicians and biologists with the different approaches and ways of working of their respective disciplines in a relaxed but highly productive manner." - Brendan O’Malley, Systems Biology Project Leader, Unilever.

The relationship between Unilever Corporate Research and Prof John King dates back to the 2005 European Study Group with Industry, where they met for the first time: at that meeting a long-term relationship was established which has since led to consultancy work and research including the current drafting of publications. In addition Unilever’s positive experiences at Study Groups inspired the Systems Biology group to sponsor an internal Maths Biology study group meeting at Unilever. This brought together Unilever researchers from the mathematical and biological sciences with leading academics, including Prof King, to work on a number of Unilever relevant problems. This has helped foster cross-disciple communication internally and initiate new projects utilising mathematical methods.

The project. The project looks at a multi-scale model – at the cellular and organ scale - of glucose and fat uptake; in particular the project investigates how glucose and fats are processed after eating a meal and how skeletal muscle switches from utilising one source of energy to another - that is from glucose to fats and vice versa. The research is critical in pre-diabetic people whether there is a history of resistance to insulin controlled glucose intake. In such insulin resistance states this fuel switching ability is impaired leading to inappropriate responses to post-meal nutrients. The goal of this project is to use the models developed to improve Unilever understanding of the mechanistic drivers of metabolic inflexibility particularly with regard to the interaction between adipose and muscle tissue.

The mathematics involved in the study is based on an ODE multi-scale model. Coupled differential equations will be used first to develop cellular models of skeletal muscle fuel utilisation which will then be incorporated into a multi-scale integrative physiological model of lipid and glucose metabolism.

How the project fits in Unilever’s research plans. This research will be continued through an Industrial CASE project based at the University of Nottingham and in collaboration with Unilever Corporate Research, where other Unilever long term research projects are developed. It sits within a wider project at Unilever – Systems Biology of Lipid Metabolism - whose scope is to identify novel dietary and lifestyle interventions that can improve heart health using the integrated approaches of systems biology.

As one of the world’s largest food companies, Unilever meets everyday needs for nutrition and add vitality to the life of its consumers. Through this work Unilever aims to develop an improved understanding of the mechanistic drivers of metabolic inflexibility and inform future experimental studies and dietary & lifestyle intervention strategies. These insights can help Unilever design new products that improve the health and vitality of its consumers. By better understanding the ultimate switch-line between glucose and fats utilisation and where the switch goes wrong, the value of this CASE project is to reduce cardiovascular disease (note: 36% of population die from CVD each year in the UK, accordingly with the BHF) and to improve people’s heart health through appropriate changes in an individuals diet and lifestyle.