Exploring the Combined Effect of High‐Fat High‐Sugar Diets and Volumetric Muscle Injury on Skeletal Muscle Metabolic and Contractile Function in Mice

Abstract

INTRODUCTIONVolumetric muscle loss (VML) injuries due to trauma or surgery cannot fully recover muscle mass and function, resulting in long‐term disability. Western diets, i.e., high‐fat, high‐sugar (HFHS) diets, promote metabolic stress and are associated with impaired skeletal muscle contractile function. The objective of this study was to investigate the extent to which a HFHS diet affected the pathophysiology following a VML injury as diet and disability may influence the effectiveness of rehabilitation. To determine the combined effects of HFHS diet and VML injury on skeletal muscle, metabolic and muscle contractile function was assessed. We hypothesized that a HFHS diet would worsen skeletal muscle metabolic and contractile function after VML injury.METHODSMale C57BL/6 mice (N=23) were randomly divided into four groups: Normal Chow (NC), High‐Fat High‐Sugar (HFHS), Volumetric Muscle Loss (VML), Volumetric Muscle Loss plus High‐Fat High‐Sugar (VML+HFHS). At age 12 weeks, VML animals underwent unilateral VML surgery to the ankle plantarflexors (gastrocnemius, plantaris, soleus muscles). HFHS groups received 60% high‐fat diet and 11% high‐fructose corn syrup for 8 weeks ad libitum. Oxygen respiration and electron conductance of mitochondria within permeabilized gastrocnemius muscle fibers and peak‐isometric torque of the ankle plantarflexors were measured to assess skeletal muscle metabolic and contractile function, respectively. Data were analyzed using a two‐way ANOVA to detect significant interactions between diet and injury, or in the absence of a significant interaction, the main effects of diet or injury.RESULTSIndependent of injury, mice on HFHS diet had 51% greater body mass compared to mice on NC (p<0.001). Additionally, mice on HFHS diet had less endurance capacity on a treadmill test compared to NC, independent of injury (77% less distance covered, p<0.001). Peak‐isometric torque was 6% less in HFHS mice, independent of injury (p=0.011) and peak‐isometric torque was 20% less in VML‐injured mice, independent of diet (p<0.01). There was a significant interaction between diet and injury for permeabilized muscle fiber oxygen respiration (p=0.016) where NC mice had greater oxygen respiration compared to HFHS, VML, and VML+HFMS mice. Electron conductance was 32% less in mice on HFHS diet, independent of injury (p<0.001) and 20% less in VML‐injured mice, independent of diet (p<0.001).CONCLUSIONThe current study indicates that both HFHS diet and VML injury have detrimental consequences on skeletal muscle contractile and metabolic function. Ongoing and future research is needed to determine the extent to which HFHS diets influence skeletal muscle plasticity and if diet impacts the effectiveness of rehabilitation strategies for VML‐injured skeletal muscle.