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Glucose Uptake and Triacylglycerol Synthesis Are Increased in Barth Syndrome Lymphoblasts

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Lipids

Abstract

Barth syndrome (BTHS) is an X-linked genetic disease resulting in loss of cardiolipin (Ptd2Gro). Patients may be predisposed to hypoglycemia and exhibit increases in whole-body glucose disposal rates and a higher fat mass percentage. We examined the reasons for this in BTHS lymphoblasts. BTHS lymphoblasts exhibited a 60% increase (p < 0.004) in 2-[1,2-3H(N)]deoxy-d-glucose uptake, a 40% increase (p < 0.01) in glucose transporter-3 protein expression, an increase in phosphorylated-adenosine monophosphate kinase (AMPK) and a 58% increase (p < 0.001) in the phosphorylated-AMPK/AMPK ratio compared to controls. In addition, BTHS lymphoblasts exhibited a 90% (p < 0.001) increase in d-[U-14C]glucose incorporated into 1,2,3-triacyl-sn-glycerol (TAG) and a 29% increase (p < 0.025) in 1,2-diacyl-sn-glycerol acyltransferase-2 activity compared to controls. Thus, BTHS lymphoblasts exhibit increased glucose transport and increased glucose utilization for TAG synthesis. These results may, in part, explain why BTHS patients exhibit an increase in whole-body glucose disposal rates, may be predisposed to hypoglycemia and exhibit a higher fat mass percentage.

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Abbreviations

BTHS:

Barth syndrome

TAZ :

Tafazzin

Ptd2Gro:

Cardiolipin

2-[3H]DG:

2-[1,2-3H(N)]deoxy-d-glucose

GLUT1:

Glucose transporter-1

GLUT3:

Glucose transporter-3

DAG:

1,2-Diacyl-sn-glycerol

DGAT-2:

1,2-Diacyl-sn-glycerol acyltransferase-2

TAG:

1,2,3-Triacyl-sn-glycerol

PtdGro:

Phosphatidylglycerol

PtdCho:

Phosphatidylcholine

PtdEtn:

Phosphatidylethanolamine

PtdSer/PtdIns:

Phosphatidylserine/phosphatidylinositol

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Acknowledgements

Supported by the Barth Syndrome Foundation of Canada/USA and the National Sciences and Engineering Research Council [RGPIN/03640-2014] (to GMH), a Research Manitoba/CHRIM Studentship (to EMM), and a CHRIM summer studentship (to JCZ). GMH is the Canada Research Chair in Molecular Cardiolipin Metabolism.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB, R3E 0W3, Canada

    Edgard M. Mejia, James C. Zinko, Kristin D. Hauff, Fred Y. Xu & Grant M. Hatch

  2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

    Kristin D. Hauff

  3. Department of Physiology and Pathophysiology, DREAM Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada

    Amir Ravandi

  4. Biochemistry and Medical Genetics, Center for Research and Treatment of Atherosclerosis, DREAM Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada

    Grant M. Hatch

Authors
  1. Edgard M. Mejia
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  2. James C. Zinko
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  3. Kristin D. Hauff
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  4. Fred Y. Xu
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  5. Amir Ravandi
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  6. Grant M. Hatch
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Correspondence to Grant M. Hatch.

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Mejia, E.M., Zinko, J.C., Hauff, K.D. et al. Glucose Uptake and Triacylglycerol Synthesis Are Increased in Barth Syndrome Lymphoblasts. Lipids 52, 161–165 (2017). https://doi.org/10.1007/s11745-017-4232-7

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  • DOI: https://doi.org/10.1007/s11745-017-4232-7

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