Abstract
<b>PURPOSE:</b> Critically ill patients tend to be given enteral nutrition continuously, which does not represent the natural feeding pattern of humans. Skeletal muscle plays a central role in metabolising ingested nutrients, yet no human research has explored variation in this tissue across 24-h in response to divergent feeding patterns. This study examined the impact of Continuous or Bolus enteral feeding patterns on the 24-h skeletal muscle transcriptome, autophagic flux in isolated neutrophils, and circulating metabolites/hormones.
<b>METHODS:</b> 18 healthy adults (2F/16M, mean ± SD: age: 26 ± 8 y; BMI: 23.5 ± 2.3 kg·m-2) rested in a laboratory for 37 hours with all data collected in the final 24 hours of this period (i.e., 0800 - 0800 h). Participants were randomized to receive their 24-h nutrition Continuously (8 M/1F; 1.3 ± 0.1 kcal·min-1) or in two equal Bolus feeds (8 M;1F; 31 ± 5 kcal·min-1). Skeletal muscle biopsies were collected every 4-h from 1200 h with hourly blood samples and a sleep opportunity from 2200-0700 h. Assessment of autophagic flux was carried out by Flow Cytometry in blood samples collected at 2000 h and 0000 h.
<b>RESULTS:</b> Bolus feeding resulted in higher exposure to insulin (2.48 ± 1.47 vs 0.56 ± 0.36 nmol·L-1·24 h; p = 0.001), and GLP-1 (336 ± 75 versus 154 ± 93 pmol·L-1·24 h; p < 0.01) compared to Continuous feeding. Autophagic flux when fed Continuously was 1666 ± 1716 LC3-B MFI·30 min-1 at 2000 h & 2201 ± 1746 LC3-B MFI·30 min-1vs 845 ± 843 LC3-B MFI·30 min-1 at 2000 h & 1256 ± 844 LC3-B MFI·30 min-1 at 0000 h when fed in Bolus. 24-h rhythms in skeletal muscle were most apparent with Continuous feeding whereas 12-h rhythms were more apparent with Bolus feeding. Continuous feeding resulted in greater amplitude of clock genes relative to Bolus feeding. Feeding pattern also altered patterns of metabolic transcripts such as PDK4.
<b>CONCLUSIONS:</b> Differences in RNA expression were apparent between feeding conditions with greater amplitude of some core clock genes with Continuous feeding. In the circulation, Bolus feeding is characterised by a more typical physiological feeding response, as seen in circulating insulin, and GLP-1 compared to Continuous feeding. Continuous enteral feeding may not be sufficient to induce a meaningful metabolic response and therefore could alter metabolic regulation during longer periods of bed rest.