Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C055

Oral Communications

Diet-induced obesity impairs muscle stem cell recruitment patterns and induces oxidative stress in skeletal muscle which are mitigated by CD36 deletion

S. Verpoorten1, A. Matsakas1, P. Sfyri1

1. Hull York Medical School, Hull, East Riding of Yorkshire, United Kingdom.


Introduction: Muscle stem cells, called satellite cells (SC), are of crucial importance for muscle regeneration. Preliminary evidence suggests that diet-induced obesity (DIO) may have a negative impact on SC function, muscle redox homeostasis and subsequently skeletal muscle repair. Recent findings indicate that ectopic lipid accumulation not only leads to metabolic deficits but contributes to lipotoxicity and increased oxidative stress. Given the importance of lipid accumulation in the context of impaired muscle metabolism, the fatty acid translocase CD36 has recently received a great amount of attention as a possible target to improve muscle health in obese conditions. However, the underlying protective mechanism of abrogated CD36 signalling is still unknown. Here we investigated the impact of CD36-deficiency in skeletal muscle oxidative stress and stem cell function in response to DIO. Methods: CD36-deficient and wild-type (WT) mice were administered either a standard chow or a high-fat (HF; 45% fat) diet for 12 weeks. Single muscle fibres and muscle tissue were studied for stem cell recruitment (i.e. activation, proliferation and differentiation patterns), fibre type composition and markers of oxidative stress. Lipid accumulation was assessed in skeletal muscle and the liver. Results: We report here that CD36-deficient mice were protected against adiposity, intramuscular lipid accumulation and exhibited reduced expression for markers of oxidative stress. Despite similar baseline SC number among experimental groups, obese mice showed impaired SC proliferation and differentiation. Interestingly, CD36 deficiency rescued SC proliferation, but led to impaired differentiation, independent of diet. Additionally, CD36-deficient mice showed increased lipid infiltration in the liver in response to HF diet. Conclusions: Using the ex vivo model of single muscle fibres we conclude that DIO impairs muscle stem cell proliferation and differentiation which is partially rescued by CD36 deletion. Moreover, loss of CD36 decreases intramuscular lipid accumulation and attenuates skeletal muscle oxidative stress, but leads to hepatic steatosis. It remains to be established whether CD36 inhibition represents a therapeutic target to tackle obesity and related metabolic disorders.

Where applicable, experiments conform with Society ethical requirements