It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2 mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2 mice, treated Pcyt2 mice, and Pcyt2 mice. The major positive effect of choline supplementation on IR muscle was the reduction of glucose utilization for FA and triglyceride (TAG) synthesis and increased muscle glucose storage as glycogen. Choline reduced the expression of genes for FA and TAG formation (Scd1, Fas, Srebp1c, Dgat1/2), upregulated the genes for FA oxidation (Cpt1, Pparα, Pgc1α), and had minor effects on phospholipid and lipolysis genes. Pcyt2 muscle had reduced insulin signaling (IRS1), autophagy (LC3), and choline transport (CTL1) proteins that were restored by choline treatment. Additionally, choline activated AMPK and Akt while inhibiting mTORC1 phosphorylation. These data established that choline supplementation could restore muscle glucose metabolism by reducing lipogenesis and improving mitochondrial and intracellular signaling for protein and energy metabolism in insulin resistant Pcyt2 deficient mice.

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Understanding the processing of tactile information is crucial for the development of biofeedback interventions that target cutaneous mechanoreceptors. Mechanics of the skin have been shown to influence cutaneous tactile sensitivity. It has been established that foot skin mechanics are altered due to foot posture, but whether these changes affect cutaneous sensitivity are unknown. The purpose of this study was to investigate the potential effect of posture-mediated skin deformation about the ankle joint on perceptual measures of foot skin sensitivity. Participants (N = 20) underwent perceptual skin sensitivity testing on either the foot sole (N = 10) or dorsum (N = 10) with the foot positioned in maximal dorsiflexion/toe extension, maximal plantarflexion/toe flexion, and a neutral foot posture. Perceptual tests included touch sensitivity, stretch sensitivity, and spatial acuity. Regional differences in touch sensitivity were found across the foot sole (p < 0.001) and dorsum (p < 0.001). Touch sensitivity also significantly increased in postures where the skin was compressed (p = 0.001). Regional differences in spatial acuity were found on the foot sole (p = 0.002) but not dorsum (p = 0.666). Spatial acuity was not significantly altered by posture across the foot sole and dorsum, other than an increase in sensitivity at the medial arch in the dorsiflexion posture (p = 0.006). Posture*site interactions were found for stretch sensitivity on the foot sole and dorsum in both the transverse and longitudinal directions (p < 0.005). Stretch sensitivity increased in postures where the skin was pre-stretched on both the foot sole and dorsum. Changes in sensitivity across locations and postures were believed to occur due to concurrent changes in skin mechanics, such as skin hardness and thickness, which follows our previous findings. Future cutaneous biofeedback interventions should be applied with an awareness of these changes in skin sensitivity, to maximize their effectiveness for foot sole and dorsum input.