Effect of an acute prolonged overnight fast on skeletal muscle insulin and anabolic sensitivity in healthy men

Background Repeated prolonged overnight fasting enhances anabolic sensitivity and preserves myofibrillar protein synthesis. Whether a single fasting episode can enhance dietary protein-derived amino acid incorporation into skeletal muscle protein remains unclear. Objective To investigate the effect of a single 16-hour versus 10-hour overnight fast on postprandial insulin and anabolic sensitivity in humans. Methods Randomized, cross-over study. On 2 occasions, healthy participants ( n =9; age 22.6±3.5 y; BMI 24.0±2.5 kg·m -2 ; HOMA-IR 1.00±0.54) ingested a liquid meal, which consisted of specifically produced, intrinsically [1- 13 C]phenylalanine labelled milk protein (0.35 g·kg -1 body mass, bm) and dextrose (0.8 g·kg -1 bm), dissolved in 6 mL·kg -1 bm water, after either a 10-hour (Control) or 16-hour (Long OF) overnight fast. Skeletal muscle and blood samples were obtained before, during, and 3 hours after meal ingestion. Results Postprandial incorporation of dietary protein-derived [1- 13 C]phenylalanine into myofibrillar protein did not differ between Control and Long OF (0.018±0.005 vs. 0.022±0.005 Mole Percent Excess (MPE), d s =0.22, P=0.56). Forearm branched amino acid uptake iAUC [Δ (95% CI) 103 (-1618 to 1823) μmol . min -1. 180min, d s =0.05, P=0.892] and glucose uptake [Δ (95% CI) 24.7 (to -25.3 to 74.8) μmol . min -1 , η 2 p =0.16, P=0.280] also did not differ between treatments, but the postprandial serum insulin response [Δ (95% CI) -7.4 (-14.4 to -0.4) mIU . L -1 , η 2 p =0.42, P=0.042] was lower in Long OF. Conclusions A single prolonged overnight fast does not enhance postprandial skeletal muscle insulin sensitivity or dietary protein-derived amino acid incorporation into skeletal muscle protein in healthy, young adults. Whether susceptible populations such as older, insulin resistant individuals, may benefit from a more prolonged overnight fast warrants investigation. Clinical Trial Registry number ClinicalTrials.gov Identifier NCT05420181 URL of registration https://clinicaltrials.gov/study/NCT05420181?term=overnight%20fasting%0AKostas%20Tsintzas&rank=1