Methacholine (M) and resistance exercise training (RET) increase human myofibrillar protein absolute synthetic rate (MPASR) in proportion to increased nutritively perfused mass, belied by steady myofibrillar protein fractional synthetic rates (MPFSR) (LB760)

Abstract

Michael Clark identified the metabolic power of switching from non nutritive to nutritive flow but for aminoacids (AA) in human leg the situation is complex e.g. leg has ≍35% non muscle lean and fat tissue draining into femoral vein blood. Thus, measures derived from tracer exchange, including Ra, Rd and Net Protein Balance (NPB, ([AAa]‐[AAv]xF)) and MPFSR, are too imprecise to surely detect increases in MPASR unless the % increase in microvascularly perfused muscle is dominant and, or the true muscle mass is known. To research this we measured leg femoral flow (FBF, Doppler) and microvascular blood volume (MBV, CEUS) and components of MPASR groups: 10 men (23 y) fed IV D5W‐AA mix, infused with M (AJP doi: 10.1152); 10 men (72 y) studied postabsorptively and IV fed, pre and post RET (20 w). Unilateral arterial M raised fed state FBF and MBV (126±12% P<0.05; 79±30% P<0.05) causing large but non significant increases (+ ≍50% P=0.26) in NPB. Post RET men showed greater leg strength (+39% P<0.0001) and leg, appendicular and whole body muscle masses (median +1.3‐2.3%, CI 1.1‐16%; RM‐ANOVA, P<0.0001). They also showed greater fed state FBF and MBV than before (+40±11% P<0.05; +44±15% P<0.001) and NPB was larger (+40±16%, P<0.05) despite identical basal FBF and MBV. MPFSR always increased on feeding, but its doubling (P<0.001) and final value (≍0.072%/h) were constant. However for post RET men, knowledge of true DXA muscle mass, corrected for non muscle, revealed significant increases in MPASR (MPFSR x mass x [muscle protein] of 3.2 (2.5‐11.2)%, (median (CI) P<0.01). Thus, likely for M, and certainly for RET, the adaptive response to M and RET is to service fed perfused muscle by increasing AA delivery and thus MPASR.Grant Funding Source: Supported by the Dunhill Medical Trust; I acknowledge my collaborators, K Sjøberg, J P Williams and S Heymsfield, and the technical assistance of P Atherton, M Limb, B E Phillips, A Selby, K Smith and K Varadhan.