Measuring muscle protein synthesis in humans and the influence of nutritional state.

In 1982 and 2011, Clinical Science published papers that used infusion of stable isotope-labeled amino acids to assess skeletal muscle protein synthesis in the fasted and fed state and before and after a period of increased intake of omega-3 fatty acids, respectively; both of these papers have been highly cited. An overview of the study designs, key findings and novel features, and a consideration of the lasting impact of these two papers is presented. The earlier paper introduced stable isotope tracer approaches in humans that showed consuming a meal will increase whole body oxidation, synthesis, and breakdown of protein, but that protein synthesis is greater than breakdown resulting in net accumulation of protein. The paper also demonstrated that consuming a meal promotes net protein synthesis in skeletal muscle. The later paper introduced the concept that omega-3 polyunsaturated fatty acids are able to improve anabolism by reporting that 8 weeks consumption of high-dose omega-3 fatty acids by healthy young and middle-aged adults increased skeletal muscle protein synthesis during a hyperaminoacidemic-hyperinsulinemic clamp compared with what was seen during the clamp at study entry. Omega-3 fatty acids also increased the phosphorylation of important signaling proteins in muscle, including mammalian target of rapamycin, p70s6k, and Akt, during the clamp. These two papers remain relevant because they offer experimental approaches to study human (patho)physiology in different contexts, they present novel insights into the impact of nutritional state (feeding) and specific nutrients (omega-3 fatty acids) on muscle protein synthesis, and they suggest ways to explore the potential of interventions to help prevent and reverse the age-, disease-, and disuse-associated decline in muscle mass.