Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks of simulated sedentary behaviour and recovery in healthy older adults

Abstract

Older adults are at risk of physical inactivity as they encounter debilitating life events. It is not known how insulin sensitivity is affected by modest short-term physical inactivity and recovery in healthy older adults, nor how insulin sensitivity is related to changes in serum and muscle ceramide content. Healthy older adults (aged 64-82 years, five females, seven males) were assessed before (PRE), after 2 weeks of reduced physical activity (RA) and following 2 weeks of recovery (REC). Insulin sensitivity (hyperinsulinaemic-euglyceamic clamp), lean mass, muscle function, skeletal muscle subfraction, fibre-specific, and serum ceramide content and indices of skeletal muscle inflammation were assessed. Insulin sensitivity decreased by 15 ± 6% at RA (driven by men) but rebounded above PRE by 14 ± 5% at REC. Mid-plantar flexor muscle area and leg strength decreased with RA, although only muscle size returned to baseline levels following REC. Body fat did not change and only minimal changes in muscle inflammation were noted across the intervention. Serum and intramuscular ceramides (nuclear/myofibrillar fraction) were modestly increased at RA and REC. However, ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults. Short-term inactivity induced insulin resistance in older adults in the absence of significant changes in body composition (i.e. fat mass) are not related to changes in ceramides.

Physical inactivity‐induced insulin resistance: could alterations to the vasculature be to blame?

“…The primary aim of this research was to examine changes in systemic insulin sensitivity and relate changes in insulin sensitivity to the level of pro-inflammatory ceramides in skeletal muscle. Reidy et al (2018) corroborated earlier reports and found that insulin sensitivity significantly decreased following 2 weeks of physical inactivity. Interestingly, after 2 weeks of returning to a physically active state, insulin sensitivity had rebounded above baseline levels by 14%.…”

“…Reidy et al . () corroborated earlier reports and found that insulin sensitivity significantly decreased following 2 weeks of physical inactivity. Interestingly, after 2 weeks of returning to a physically active state, insulin sensitivity had rebounded above baseline levels by 14%.…”

An accumulation of muscle macrophages is accompanied by altered insulin sensitivity after reduced activity and recovery

“…Subject characteristics have been outlined previously . Healthy older adults (5F/7M, 70 ± 2 years, BMI of 26 ± 1, 92 ± 2 mg/dL resting glucose, HbA1c % 5.5 ± 0.1, 31 ± 2% fat and 49 ± 3 kg of total lean mass) participated in the study.…”

“…We recruited 12 (seven male, five female) healthy, community‐dwelling, glucose tolerant subjects from the Salt Lake City area between the ages of 60 and 85 years and with a BMI <30 kg/m 2 . Healthy subjects were recruited and screened similarly as we have previously reported . All subjects read and signed the informed consent form.…”

“…For the measurements of insulin sensitivity, subjects arrived in the morning at the CCTS after an overnight fast, completed a DXA and pQCT scan, underwent a baseline thigh muscle biopsy (below), then participated in a ~3‐hour hyperinsulinaemic‐euglycaemic clamp . To assess insulin sensitivity during the clamp, insulin was infused at a constant rate of 80 mU/m 2 /min as we have previously described . Vastus lateralis muscle biopsies (5 mm Bergström needle with manual suction) were sampled (~150 mg) on the right thigh before and then on the left thigh after the clamp for measurements of fasting and insulin‐stimulated muscle samples for immunofluorescent detection of macrophages, satellite cells and capillaries and mRNA expression of markers of inflammation.…”