Postabsorptive rates of MPS were 27% lower in ED than EB (P Ͻ 0.001), but REX stimulated MPS to rates equal to EB. Ingestion of 15 and 30 g of protein after REX in ED increased MPS ϳ16 and ϳ34% above resting EB (P Ͻ 0.02). p70 S6K Thr 389 phosphorylation increased above EB only with combined exercise and protein intake (ϳ2-7 fold, P Ͻ 0.05). In conclusion, short-term ED reduces postabsorptive MPS; however, a bout of REX in ED restores MPS to values observed at rest in EB. The ingestion of protein after REX further increases MPS above resting EB in a dose-dependent manner. We conclude that combining REX with increased protein availability after exercise enhances rates of skeletal muscle protein synthesis during short-term ED and could in the long term preserve muscle mass. body composition; fat-free mass; myofibrillar protein synthesis; weight loss ENERGY DEFICIT (ED) can be achieved through reduced energy intake and/or increased energy expenditure and subsequently leads to loss of fat mass (FM). A reduction in FM is a goal for improved health (19, 33); however, when achieved by energy restriction alone, it typically results in the concomitant weight loss comprised of ϳ25% fat-free mass (FFM) (52), of which skeletal muscle is the main component (37,39). Given that the quality and quantity of skeletal muscle is a major determinant of whole body metabolic rate and functional capacity throughout the lifespan (25), nutritional and exercise strategies to prevent or minimize loss of FFM while losing fat mass are crucial.Pasiakos et al. (41) reported a 19% reduction in basal rates of mixed-muscle protein synthesis in young healthy males and females after 10 days of ED (ϳ500 kcal/day). In contrast, a more recent study from Pasiakos et al. (40) found no decrease in rates of resting muscle protein synthesis after 30 days of moderate ED. If a potential decrease in basal rates of muscle protein synthesis was not accompanied by a concomitant reduction in muscle protein breakdown, then ED would presumably result in a marked loss of skeletal muscle protein. Indeed, prolonged ED-induced body weight loss can be comprised of up to 60% FFM (40). In contrast, exercise has been shown to attenuate the loss of lean body tissue that typically occurs with periods of ED alone (50). However, it is currently unknown whether the anabolic effects of resistance exercise (REX) are attenuated during periods of ED.Provision of dietary amino acids increases skeletal muscle protein synthesis, an effect that is enhanced by prior REX (3, 36). To date, only one study has examined whether skeletal muscle exhibits "anabolic resistance" to exercise and protein ingestion following short-term ED (40). However, in that investigation, rates of mixed-muscle protein synthesis and not myofibrillar protein synthesis (MPS; i.e., the contractile protein fraction of muscle) were measured. Furthermore, there was no examination of the impact of exercise, and the cohort under investigation was comprised mainly of males. Hence, the primary aim of the current study was...