The Impact of Short and Long-Term Inactivity on Intramyocellular Lipid Content and Whole Body Insulin Resistance
Overview:
Intramyocellular lipid (IMCL) – fat stored as droplets in muscle cells - provides an important energy source for working muscle. However, when a patient has low levels of physical activity (e.g. when affected by mobility impairing conditions like osteoarthritis) and/or excessive energy intake, levels of IMCL can be high and can be used as an indicator of poor metabolic health. High levels of IMCL have been associated with insulin resistance (where the body is not stimulated by insulin to convert glucose into energy). Ultimately, this can lead to a higher risk of developing type-2 diabetes.
Previous research has not clearly separated the impact of physical inactivity and excessive energy intake on levels of IMCL and the development of insulin resistance. This project will focus on the impact of physical inactivity by studying volunteers on a strict diet, but with significantly reduced levels of inactivity. Some volunteers will be undertaking acute (3 days) and chronic (56 days) bed rest in healthy volunteers maintained on a prescribed diet. These findings will present novel insight into the relative contribution of IMCL accumulation and inactivity to the development of insulin resistance in inactivity and will significantly add to our understanding of the role that diet and physical activity have in driving poor metabolic health in humans.
Aims and Objectives:
To provide a novel insight into the relative contribution of IMCL accumulation and inactivity to the development of insulin resistance in healthy volunteers, which will add to our understanding of the mechanistic role that diet and physical activity have in driving poor metabolic health in humans.
Key Findings:
So long as the energy intake from calories consumed matches the energy expended, the fat content of muscle does not increase during inactivity. It is important to note that though we did not observe any changes in muscle fat content, we did see that inactivity rapidly impaired the ability of muscle to take up glucose from the blood in response to stimulation by insulin. This has important implications to metabolic health.
Outputs
Shur, NF, Simpson, EJ, Crossland, H, Chivaka, PK, Constantin, D, Cordon, SM, Constantin-Teodosiu, D, Stephens, FB, Lobo, DN, Szewczyk, N, Narici, M, Prats, C, Macdonald, IA, Greenhaff, PL. Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization. J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2999-3013. https://doi.org/10.1002/jcsm.13075