Isolated Murine Skeletal Muscles Utilize Pyruvate over Glucose for Oxidation

Overview

Journal Metabolomics

Publisher Springer

Specialty Endocrinology

Date 2022 Dec 8

PMID 36480060

Authors

Ram B Khattri

Jason Puglise

Terence E Ryan

Glenn A Walter

Matthew E Merritt

Elisabeth R Barton

Affiliations

Soon will be listed here.

Abstract

Introduction: Fuel sources for skeletal muscle tissue include carbohydrates and fatty acids, and utilization depends upon fiber type, workload, and substrate availability. The use of isotopically labeled substrate tracers combined with nuclear magnetic resonance (NMR) enables a deeper examination of not only utilization of substrates by a given tissue, but also their contribution to tricarboxylic acid (TCA) cycle intermediates.

Objectives: The goal of this study was to determine the differential utilization of substrates in isolated murine skeletal muscle, and to evaluate how isopotomer anlaysis provided insight into skeletal muscle metabolism.

Methods: Isolated C57BL/6 mouse hind limb muscles were incubated in oxygenated solution containing uniformly labeled C glucose, C pyruvate, or C acetate at room temperature. Isotopomer analysis of C labeled glutamate was performed on pooled extracts of isolated soleus and extensor digitorum longus (EDL) muscles.

Results: Pyruvate and acetate were more avidly consumed than glucose with resultant increases in glutamate labeling in both muscle groups. Glucose incubation resulted in glutamate labeling, but with high anaplerotic flux in contrast to the labeling by pyruvate. Muscle fiber type distinctions were evident by differences in lactate enrichment and extent of substrate oxidation.

Conclusion: Isotope tracing experiments in isolated muscles reveal that pyruvate and acetate are avidly oxidized by isolated soleus and EDL muscles, whereas glucose labeling of glutamate is accompanied by high anaplerotic flux. We believe our results may set the stage for future examination of metabolic signatures of skeletal muscles from pre-clinical models of aging, type-2 diabetes and neuromuscular disease.

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