Alcohol, Resistance Exercise, and mTOR Pathway Signaling: An Evidence-Based Narrative Review

Abstract

Skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and degradation. Several intracellular signaling pathways control this balance, including mammalian/mechanistic target of rapamycin (mTOR) complex 1 (C1). Activation of this pathway in skeletal muscle is controlled, in part, by nutrition (e.g., amino acids and alcohol) and exercise (e.g., resistance exercise (RE)). Acute and chronic alcohol use can result in myopathy, and evidence points to altered mTORC1 signaling as a contributing factor. Moreover, individuals who regularly perform RE or vigorous aerobic exercise are more likely to use alcohol frequently and in larger quantities. Therefore, alcohol may antagonize beneficial exercise-induced increases in mTORC1 pathway signaling. The purpose of this review is to synthesize up-to-date evidence regarding mTORC1 pathway signaling and the independent and combined effects of acute alcohol and RE on activation of the mTORC1 pathway. Overall, acute alcohol impairs and RE activates mTORC1 pathway signaling; however, effects vary by model, sex, feeding, training status, quantity, etc., such that anabolic stimuli may partially rescue the alcohol-mediated pathway inhibition. Likewise, the impact of alcohol on RE-induced mTORC1 pathway signaling appears dependent on several factors including nutrition and sex, although many questions remain unanswered. Accordingly, we identify gaps in the literature that remain to be elucidated to fully understand the independent and combined impacts of alcohol and RE on mTORC1 pathway signaling.

Keywords: alcohol; mTOR; myopathy; protein synthesis; resistance exercise.

Figure 1

Overview of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway and events that are inhibited (gold lightning bolts) or promoted (blue lightning bolt) by ethanol (EtOH). Phosphate groups (P) in red indicate inhibitory events; P in blue indicate activating events. Abbreviations: 4E binding protein 1 (4EBP1), AMP-activated protein kinase (AMPK), diacylglycerol kinase (DGK), diacylglycerol (DAG), eukaryotic elongation factor (eEF), eukaryotic initiation factor (eIF), GAP activity toward Rags (GATOR), insulin receptor substrate (IRS), insulin-like growth factor-1 (IGF-1), liver kinase B1 (LKB1), p70 S6 kinase 1 (S6K1), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanol (PEth), phosphatidylinositol (4,5)-bisphosphate (PIP2), phosphatidylinositol (3,4,5)-trisphosphate (PIP3), phosphoinositide 3-kinase (PI3K), phospholipase D (PLD), protein kinase B (Akt), pyruvate dehydrogenase kinase 1 (PDK1), Ras homolog enriched in brain (Rheb), ribosomal protein S6 (rpS6), tuberous sclerosis complex (TSC). Created using Biorender.com (accessed on 13 December 2022).

Figure 2

Overview of mammalian/mechanistic target of rapamycin (mTOR) signaling pathway events that are inhibited (pink lightning bolt) or promoted (green lightning bolts) by resistance exercise (RE), and known or potential impacts of ethanol (EtOH) on these changes. Phosphate groups (P) in red indicate inhibitory events; P in blue indicate activating events. Abbreviations: 4E binding protein 1 (4EBP1), AMP-activated protein kinase (AMPK), diacylglycerol kinase (DGK), diacylglycerol (DAG), eukaryotic elongation factor (eEF), eukaryotic initiation factor (eIF), GAP activity toward Rags (GATOR), insulin receptor substrate (IRS), insulin-like growth factor-1 (IGF-1), liver kinase B1 (LKB1), p70 S6 kinase 1 (S6K1), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylinositol (4,5)-bisphosphate (PIP2), phosphatidylinositol (3,4,5)-trisphosphate (PIP3), phosphoinositide 3-kinase (PI3K), phospholipase D (PLD), protein kinase B (Akt), pyruvate dehydrogenase kinase 1 (PDK1), Ras homolog enriched in brain (Rheb), ribosomal protein S6 (rpS6), tuberous sclerosis complex (TSC). Created using Biorender.com (accessed on 13 December 2022).