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AICAR inhibits oxygen consumption by intact skeletal muscle cells in culture

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Abstract

Activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) with aminoimidazole carboxamide ribonucleotide (AICAR) increases skeletal muscle glucose uptake and fatty acid oxidation. The purpose of these experiments was to utilize AICAR to enhance palmitate consumption by mitochondria in cultured skeletal muscle cells. In these experiments, we treated C2C12 myotubes or adult single skeletal muscle fibers with varying concentrations of AICAR for different lengths of time. Surprisingly, acute AICAR exposure at most concentrations (0.25–1.5 mM), but not all (0.1 mM), modestly inhibited oxygen consumption even though AICAR increased AMPK phosphorylation. The data suggest that AICAR inhibited oxygen consumption by the cultured muscle in a non-specific manner. The results of these experiments are expected to provide valuable information to investigators interested in using AICAR in cell culture studies.

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Abbreviations

ACC:

Acetyl CoA-carboxylase

AICAR:

Aminoimidazole carboxamide ribonucleotide

AMPK:

5′ Adenosine monophosphate-activated protein kinase

DM:

Differentiation media

ETC:

Electron transport chain

FCCP:

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone

FDB:

Flexor digitorum brevis

MB:

Extracellular flux measurement buffer

OCR:

Oxygen consumption rates

PA:

Sodium palmitate

SRC:

Spare respiratory capacity

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Acknowledgments

The authors wish to thank Dr(s) David Thomson, Andy Philp, Keith Baar, and John Thyfault for insightful discussions. The work was supported by grants from the National Institutes of Health AR059913 (EES), Baltimore Diabetes Research Training Center Grant (EES) (P60DK079637), Rehabilitation R&D REAP and Biomedical R&D CDA-02 from the VA Research Service (RAS). The funding sources play no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD, 21045, USA

    Espen E. Spangenburg & Kathryn C. Jackson

  2. Research Service, Maryland VA Health Care System, Baltimore, MD, 21201, USA

    Rosemary A. Schuh

  3. Department of Neurology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA

    Rosemary A. Schuh

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  1. Espen E. Spangenburg
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  2. Kathryn C. Jackson
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Correspondence to Espen E. Spangenburg.

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Spangenburg, E.E., Jackson, K.C. & Schuh, R.A. AICAR inhibits oxygen consumption by intact skeletal muscle cells in culture. J Physiol Biochem 69, 909–917 (2013). https://doi.org/10.1007/s13105-013-0269-0

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  • DOI: https://doi.org/10.1007/s13105-013-0269-0

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