Concentration or composition that is the question! How do exogenous fatty acids contribute to changes in metabolic flexibility of skeletal muscle?

Funder: 

Society for Endocrinology

Project Team:

Dr Mark C Turner

Duration:

1 March 2021 until 1 March 2022

Project overview

Excess levels of fat in skeletal muscle has been suggested to contribute to non-communicable diseases such as obesity and type 2 diabetes mellitus. As a result, there is significant interest in how skeletal muscle is able to manage excess fat importantly, how excess fat contributes to the development of metabolic disease in skeletal muscle. Individual fats exert distinct effects on skeletal muscle therefore replicating both the physiological composition and concentrations of fat in vitro, is crucial in understanding their impact on skeletal muscle metabolism.

In order to investigate the response of skeletal muscle to fat, this project will use Real-Time Cell Metabolic Analysis to establish how physiological and pathophysiological concentrations of FA impact mitochondrial function, capacity and substrate utilisation in human skeletal muscle cells.

Project objectives

The objectives of this project are:

• To establish changes in the metabolic phenotype, mitochondrial function and capacity of skeletal muscle cells exposed to physiological and pathophysiological concentrations and composition of lipids.
• To understand how increasing concentrations of lipids alters skeletal muscle cell substruate utilisation?
• To establish how lipids affect the expression of genes and proteins which underpin metabolic function in skeletal muscle.

Impact statement

By addressing the fundamental question of ‘is the type or quantity of fat the main contributor to metabolic dysfunction in skeletal muscle?’ this project will enhance our understanding of the paradoxical findings within the literature regarding the role of fat in the aetiology of obesity and type 2 diabetes. Long term, this project will enhance our understanding of how pharmacological and lifestyle interventions can be used effectively as theraptuic interventions for patients with obesity and type 2 diabetes.

Outputs

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