Alcohol Alters Skeletal Muscle Bioenergetic Function: A Scoping Review

Abstract

Bioenergetic pathways uniquely support sarcomere function which, in turn, helps to maintain functional skeletal muscle (SKM) mass. Emerging evidence supports alcohol (EtOH)-induced bioenergetic impairments in SKM and muscle precursor cells. We performed a scoping review to synthesize existing evidence regarding the effects of EtOH on SKM bioenergetics. Eligible articles from six databases were identified, and titles, abstracts, and full texts for potentially relevant articles were screened against inclusion criteria. Through the search, we identified 555 unique articles, and 21 met inclusion criteria. Three studies investigated EtOH effects on the adenosine triphosphate (ATP)-phosphocreatine (PCr) system, twelve investigated EtOH effects on glycolytic metabolism, and seventeen investigated EtOH effects on mitochondrial metabolism. Despite increased ATP-PCr system reliance, EtOH led to an overall decrease in bioenergetic function through decreased expression and activity of glycolytic and mitochondrial pathway components. However, effects varied depending on the EtOH dose and duration, model system, and sample type. The results detail the EtOH-induced shifts in energy metabolism, which may adversely affect sarcomere function and contribute to myopathy. These findings should be used to develop targeted interventions that improve SKM bioenergetic function, and thus sarcomere function, in people with Alcohol Use Disorder (AUD). Key areas in need of further investigation are also identified.

Keywords: alcohol misuse; bioenergetics; ethanol; exercise; glycolysis; metabolism; mitochondria; myoblasts; phosphagen; skeletal muscle.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram showing an overview of the study selection process.

Figure 2

Summary of EtOH-induced ATP-PCr system changes in muscle precursor cells and whole skeletal muscle (SKM) observed in studies included in this review. Abbreviations: ADP: adenosine diphosphate; ATP: adenosine triphosphate; ATP-PCr: ATP-phosphocreatine (phosphagen) system; CK: creatine kinase; Cr: creatine; PCr: phosphocreatine.

Figure 3

Summary of effects of EtOH on glycolytic metabolism in (A) muscle precursor cells (MPCs) and (B) whole skeletal muscle (SKM) or SKM fibers observed in studies included in this review. Abbreviations: 1,3-BPG: 1,3-bisphosphoglycerate; ADP: adenosine diphosphate; ALD: aldolase; ATP: adenosine triphosphate; DHAP: dihydroxyacetone phosphate; F-1,6-P₂: fructose-1,6-biphosphate; F-2,6-P₂: fructose-2-6-bisphosphate; F-6-P: fructose-6-phosphate; G-1-P: glucose-1-phosphate; G-1,6-P₂: glucose-1,6-bisphosphate; G-3-P: glyceraldehyde 3-phosphate; G-6-P: glucose-6-phosphate; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; HK: hexokinase; LDH: lactate dehydrogenase; NAD⁺: nicotinamide adenine dinucleotide (oxidized); NADH: nicotinamide adenine dinucleotide (reduced); PEP: phosphoenolpyruvate; PFK: phosphofructokinase; PG: phosphatidylglycerol; PGI: phosphoglucose isomerase; PK: pyruvate kinase.

Figure 4

Summary of effects of EtOH on conversion of pyruvate and fatty acids to acetyl CoA in muscle precursor cells (MPCs) and whole skeletal muscle (SKM) that were observed in studies included in this review. Abbreviations: CD36: cluster of differentiation 36; CoA: coenzyme A; CPT: carnitine palmitoyltransferase; EtOH: ethanol; HAD: β-hydroxyacyl-CoA dehydrogenase; LCFA: long chain fatty acid; MitoPC: mitochondrial pyruvate carrier; NAD⁺: nicotinamide adenine dinucleotide (oxidized); NADH: nicotinamide adenine dinucleotide (reduced); PDH: pyruvate dehydrogenase; PDK: pyruvate dehydrogenase kinase; VDAC: voltage-dependent anion channel.

Figure 5

Summary of effects of EtOH on the TCA cycle in (A) muscle precursor cells (MPCs) and (B) whole skeletal muscle (SKM) observed in studies included in this review. Abbreviations: ACON: aconitase; CoA: coenzyme A; CS: citrate synthase; EtOH: ethanol; FAD: flavin adenine dinucleotide (oxidized); FADH₂: flavin adenine dinucleotide (reduced); ICDH: isocitrate dehydrogenase; NAD⁺: nicotinamide adenine dinucleotide (oxidized); NADH: nicotinamide adenine dinucleotide (reduced); SDH: succinate dehydrogenase; TCA: tricarboxylic acid.

Figure 6

Summary of effects of EtOH on ETC components in (A) muscle precursor cells (MPCs) and (B) whole skeletal muscle (SKM) observed in studies included in this review. Abbreviations: ADP: adenosine diphosphate; ATP: adenosine triphosphate; Cyt: cytochrome; ETC: electron transport chain; EtOH: ethanol; FAD: flavin adenine dinucleotide (oxidized); FADH₂: flavin adenine dinucleotide (reduced); I, II, III, or IV: ETC complexes I–IV; IMS: intermembrane space; LCFA: long chain fatty acid; NAD⁺: nicotinamide adenine dinucleotide (oxidized); NADH: nicotinamide adenine dinucleotide (reduced); Ox Phos: oxidative phosphorylation.

Figure 7

Summary of effects of EtOH on mitochondrial content and bioenergetic health markers in muscle precursor cells and whole skeletal muscle observed in studies included in this review. Abbreviations: Δψ_m: mitochondrial membrane potential (SKM); ADP: adenosine diphosphate; ATP: adenosine triphosphate; EtOH: ethanol; Mito: mitochondria; ROS: reactive oxygen species; Synth.: synthase; + or −: positive or negative charges; solid ↑: increased; solid ↓: decreased.

Figure 8

Schematic representation of the global effects of EtOH on mitochondrial metabolism in muscle precursor cells and whole skeletal muscle that were observed in studies included in this review. Abbreviations: ACON: aconitase; ADP: adenosine diphosphate; ATP: adenosine triphosphate; CD36: cluster of differentiation 36; CoA: coenzyme A; CPT: carnitine palmitoyltransferase; CS: citrate synthase; Cyt: cytochrome; ETC: electron transport chain; EtOH: ethanol; FAD: flavin adenine dinucleotide (oxidized); FADH₂: flavin adenine dinucleotide (reduced); HAD: β-hydroxyacyl-CoA dehydrogenase; I, II, III, or IV: ETC complexes I–IV; ICDH: isocitrate dehydrogenase; IMS: intermembrane space; LCFA: long chain fatty acid; MitoPC: mitochondrial pyruvate carrier; NAD⁺: nicotinamide adenine dinucleotide (oxidized); NADH: nicotinamide adenine dinucleotide (reduced); Ox Phos: oxidative phosphorylation; PDH: pyruvate dehydrogenase; SDH: succinate dehydrogenase; TCA: tricarboxylic acid; VDAC: voltage-dependent anion channel.