In vivo magnetic resonance of hyperpolarized [¹³C₁]pyruvate: Metabolic dynamics in stimulated muscle

The metabolic status of muscle changes according to the energetic demands of the organism. Two key regulators of these changes include exercise and insulin, with exercise eliciting catabolic expenditure within seconds and insulin enabling anabolic energy investment over minutes to hours. This study explores the potential of time-resolved hyperpolarized dynamic ¹³C spectroscopy to characterize the in vivo metabolic phenotype of muscle during functional and biochemical insulin-induced stimulation of muscle. Using [¹³C₁]pyruvic acid as a tracer, we find that despite the different time scales of these forms of stimulation, increases in pyruvate label transport and consumption and concomitant increases in initial rates of the tracer metabolism to lactate were observed for both stimuli. By contrast, rates of tracer metabolism to labeled alanine increased incrementally for insulin but remained unchanged following exercise-like muscle stimulation. Kinetic analysis revealed that branching of the hyperpolarized [¹³C]pyruvate tracer between lactate and alanine provides significant tissuespecific biomarkers that distinguish between anabolic and catabolic fates in vivo according to the routing of metabolites between glycolytic and amino acid pathways.