Elevated miR-194-5p Expression during Short-Term Energy Deficit Attenuates Postexercise Muscle Protein Synthesis by...

Consuming protein with additional energy as essential amino acid (EAA), and not carbohydrate, has recently been shown to result in greater postexercise muscle protein synthesis (MPS) during energy deficit (DEF). However, the molecular underpinnings governing these changes in MPS are unclear.

This study examined the effects of consuming EAA-enriched whey with added EAA (+EAA) or carbohydrate (+CHO) on skeletal muscle microRNA (miRNA) after exercise in energy balance (BAL) and DEF.

Seventeen adults completed a randomized, double-blind 2-way mixed model study, consuming 5-d of BAL and DEF (-30 ± 3% energy requirements) diets separated by ≥7-d. On day 6 of each condition, volunteers consumed either a +EAA (304 kcal, 56 g protein, 48 g EAA, 17 g carbohydrate, 2 g fat, n = 8) or +CHO (311 kcal, 34 g protein, 24 g EAA, 40 g carbohydrate, 2 g fat, n = 9) drink after 60-min of load carriage (59 ± 4% peak oxygen uptake) and step ups (9 sets × 16 repetitions). miRNA (microarray RT-qPCR) expression was determined at rest (PRE) and 4-h into recovery (REC). Change in MPS (²H₅-phenylalanine; previously reported) was determined during REC.

Three miRNA (miR-194-5p, miR-324-3p, let-7i-5p) increased (P < 0.05, false detection rate < 0.1) from BAL to DEF, regardless of time and treatment. During DEF REC, miR-194-5p was inversely associated with ΔMPS (r = -0.59, P = 0.03). In vitro overexpression of miR-194-5p in C2C12 skeletal muscle cells elicited lower p-mTOR^Ser2448, p-p70S6K^Thr424/421, and p-rpS6^Ser235/236 than CON.

These data provide a molecular basis for postexercise anabolic resistance during DEF. The increase in miR-194-5p from BAL to DEF likely attenuates postexercise MPS by downregulating anabolic signaling, an effect not mediated by consuming additional EAA or carbohydrate. This trial was registered at clinicaltrials.gov as NCT04621175.