Acute effects of a ketone monoester, whey protein, or their co-ingestion on mTOR trafficking and protein-protein co-localization in human skeletal muscle.

We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their co-ingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their co-ingestion on mTOR-related protein-protein co-localization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24.2±4.1 y) ingested either: 1) 0.36 g ∙ kg-1 bodyweight of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET+PRO). Muscle biopsies were obtained in the overnight postabsorptive state (basal conditions), and at 120- and 300-minutes in the postprandial period for immunofluorescence assessment of protein translocation and co-localization of mTOR-related signaling molecules. All treatments resulted in a significant (Interaction: P <0.0001) decrease in tuberous sclerosis complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) co-localization at 120-minutes vs. basal; however, the decrease was sustained at 300-minutes vs. basal ( P <0.0001) only in KET+PRO. PRO and KET+PRO increased (Interaction: P <0.0001) mTOR-Rheb co-localization at 120-minutes vs. basal; however, KET+PRO resulted in a sustained increase in mTOR-Rheb co-localization at 300-minutes that was greater than KET and PRO. Treatment intake increased mTOR-wheat germ agglutinin (WGA) co-localization at 120- and 300-minutes (Time: P =0.0031), suggesting translocation toward the fiber periphery. These findings demonstrate that ketone monoester intake can influence the spatial mechanisms involved in the regulation of mTORC1 in human skeletal muscle.