High-protein diet with excess leucine prevents inactivity-induced insulin resistance in women

Background and aims: Muscle inactivity leads to muscle atrophy and insulin resistance. The branched-chain amino acid (BCAA) leucine interacts with the insulin signaling pathway to modulate glucose metabolism. We have tested the ability of a high-protein BCAA-enriched diet to prevent insulin resistance during long-term bed rest (BR). Methods: Stable isotopes were infused to determine glucose and protein kinetics in the postabsorptive state and during a hyperinsulinemic-euglycemic clamp in combination with amino acid infusion (Clamp + AA) before and at the end of 60 days of BR in two groups of healthy, young women receiving eucaloric diets containing 1 g of protein/kg per day (n = 8) or 1.45 g of protein/kg per day enriched with 0.15 g/kg per day of BCAAs (leucine/valine/isoleucine = 2/1/1) (n = 8). Body composition was determined by Dual X-ray Absorptiometry. Results: BR decreased lean body mass by 7.6 ± 0.3 % and 7.2 ± 0.8 % in the groups receiving conventional or high protein-BCAA diets, respectively. Fat mass was unchanged in both groups. At the end of BR, percent changes of insulin-mediated glucose uptake significantly (p = 0.01) decreased in the conventional diet group from 155 ± 23 % to 84 ± 10 % while did not change significantly in the high protein-BCAA diet group from 126 ± 20 % to 141 ± 27 % (BR effect, p = 0.32; BR/diet interaction, p = 0.01; Repeated Measures ANCOVA). In contrast, there were no BR/diet interactions on proteolysis and protein synthesis Clamp + AA changes in the conventional diet and the high protein-BCAA diet groups. Conclusion: A high protein-BCAA enriched diet prevented inactivity-induced insulin resistance in healthy women.