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Cited by 276Mitochondrial Function and PathologyMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

Galactose Enhances Oxidative Metabolism and Reveals Mitochondrial Dysfunction in Human Primary Muscle Cells

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Aguer, Céline, Gambarotta, Daniela, Mailloux, Ryan J., Moffat, Cynthia, Dent, Robert, McPherson, Ruth, Harper, Mary-Ellen·2011·PLoS ONE
DOI 10.1371/journal.pone.0028536PMC PMC3240634
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Abstract

BACKGROUND: Human primary myotubes are highly glycolytic when cultured in high glucose medium rendering it difficult to study mitochondrial dysfunction. Galactose is known to enhance mitochondrial metabolism and could be an excellent model to study mitochondrial dysfunction in human primary myotubes. The aim of the present study was to 1) characterize the effect of differentiating healthy human myoblasts in galactose on oxidative metabolism and 2) determine whether galactose can pinpoint a mitochondrial malfunction in post-diabetic myotubes. METHODOLOGY/PRINCIPAL FINDINGS: Oxygen consumption rate (OCR), lactate levels, mitochondrial content, citrate synthase and cytochrome C oxidase activities, and AMPK phosphorylation were determined in healthy myotubes differentiated in different sources/concentrations of carbohydrates: 25 mM glucose (high glucose (HG)), 5 mM glucose (low glucose (LG)) or 10 mM galactose (GAL). Effect of carbohydrates on OCR was also determined in myotubes derived from post-diabetic patients and matched obese non-diabetic subjects. OCR was significantly increased whereas anaerobic glycolysis was significantly decreased in GAL myotubes compared to LG or HG myotubes. This increased OCR in GAL myotubes occurred in conjunction with increased cytochrome C oxidase activity and expression, as well as increased AMPK phosphorylation. OCR of post-diabetic myotubes was not different than that of obese non-diabetic myotubes when differentiated in LG or HG. However, whereas GAL increased OCR in obese non-diabetic myotubes, it did not affect OCR in post-diabetic myotubes, leading to a significant difference in OCR between groups. The lack of an increase in OCR in post-diabetic myotubes differentiated in GAL was in relation with unaltered cytochrome C oxidase activity levels or AMPK phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that differentiating human primary myoblasts in GAL enhances aerobic metabolism. Because this cell culture model elicited an abnormal response in cells from post-diabetic patients, it may be useful in further studies of the molecular mechanisms of mitochondrial dysfunction.

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  • APOE4 astrocytes exhibit reduced mitochondrial metabolism as measured by MTT.

    “the APOE4 astrocytes exhibit reduced mitochondrial metabolism as measured by MTT20,36 (Fig. 5c)”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [36]

    The Materials and Methods section (‘Cell redox environment’) uses MTT to assess cellular redox state, and the Discussion explains how MTT reduction reflects cellular NAD(P)H. The paper studies human muscle cells, not APOE4 astrocytes, and does not report reduced mitochondrial metabolism in those cells. It supports the use of MTT as a metabolic readout, but not the stated APOE4 finding. (LLM, conf=0.87)

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Authors
Aguer, C., Gambarotta, D., Mailloux, R. J., Moffat, C., Dent, R., McPherson, R., & Harper, M.-E.
Affiliations
  • University of Ottawa (CA)
  • Ottawa Hospital (CA)
  • Ottawa Heart Institute (CA)
Corresponding author
Harper, Mary-Ellen
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-12-15
Volume
6
Issue
12
Pages
e28536
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0028536
PMC
PMC3240634
OpenAlex
W2004145886
Cited by
276
References
8
Citations by year
2026: 19 · 2025: 21 · 2024: 27 · 2023: 24 · 2022: 19 · 2021: 29 · 2020: 27 · 2019: 21 · 2018: 19 · 2017: 18 · 2016: 15 · 2015: 7 · 2014: 14 · 2013: 12 · 2012: 2
FWCI
3.41
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Canadian Institutes of Health Research
  • Institute of Nutrition, Metabolism and Diabetes
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
galactose, mitochondrial dysfunction, oxidative metabolism, myogenesis, oxygen consumption rate, aerobic metabolism, glycolysis, cytochrome c oxidase, AMPK phosphorylation, type 2 diabetes, obesity, carbohydrate metabolism
MeSH terms
Adenosine Triphosphate, Adenylate Kinase, Adult, Aerobiosis, Cell Differentiation, Cells, Cultured, Culture Media, Electron Transport Complex IV, Diabetes Mellitus, Female, Galactose, Glucose, Humans, Male, Mitochondria, Oxidation-Reduction, Phosphorylation, Biomarkers, Muscle Fibers, Skeletal, Muscle Cells

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