The effects of 5 days of bed rest on insulin sensitivity and ceramide biosynthesis expression in skeletal muscle of older adults

Physical inactivity in older adults is a risk factor for developing glucose intolerance and impaired skeletal muscle function. Elevated ceramide levels have been linked to metabolic disruption and toll-like receptor 4 (TLR4) signaling. The purpose of this study is to determine if short-term physical inactivity, bed rest, affects insulin sensitivity and skeletal muscle levels of ceramide biosynthesis gene expression in older adults. We hypothesize that physical inactivity will increase skeletal ceramide biosynthesis expression and decrease Akt phosphorylation in older adults. Secondly, 5 days of bed rest will decrease insulin sensitivity and glucose tolerance and increase NEFA circulation levels in older adults. Therefore, we recruited 9 healthy male and female older adult participants (age range: 60-75). Participants underwent a 5-day bed rest experiment in the Center for Clinical and Translational Science at the University of Utah Hospital. Muscle biopsies and fasting blood samples were collected. OGTTs were performed. We found that 5 days of bed rest in older adults resulted in whole body glucose dysregulation, impaired skeletal muscle insulin signaling, and upregulation of markers of ceramide biosynthesis (P<0.05). Post bed rest TLR4 abundance was tightly correlated with impaired post-prandial insulin and glucose levels. In conclusion, 5 days of bed rest in older adults can increase SPT2 protein expression and impair skeletal muscle insulin signaling via Akt phosphorylation. TLR4-mediated SPT2 expression after bed rest may be an important link between physical inactivity and glucose intolerance.