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Original Research

Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity

  1. Mitch T. Sitnick1,
  2. Mahesh K. Basantani1,
  3. Lingzhi Cai1,
  4. Gabriele Schoiswohl1,
  5. Cynthia F. Yazbeck1,
  6. Giovanna Distefano1,
  7. Vladimir Ritov1,
  8. James P. DeLany1,
  9. Renate Schreiber2,
  10. Donna B. Stolz3,
  11. Noah P. Gardner4,
  12. Petra C. Kienesberger5,
  13. Thomas Pulinilkunnil5,
  14. Rudolf Zechner3,
  15. Bret H. Goodpaster1,
  16. Paul Coen1,6 and
  17. Erin E. Kershaw1⇑
  1. 1Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
  2. 2Institute of Molecular Biosciences, University of Graz, Graz, Austria
  3. 3Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania
  4. 4Novartis Institute of Biomedical Research, Cambridge, Massachusetts
  5. 5Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick, Saint John, New Brunswick, Canada
  6. 6Department of Health and Physical Activity, University of Pittsburgh, Pittsburgh, Pennsylvania.
  1. Corresponding author: Erin E. Kershaw, kershawe{at}pitt.edu.
  1. M.T.S., M.K.B., and L.C. contributed equally to this work.

Diabetes 2013 Oct; 62(10): 3350-3361. https://doi.org/10.2337/db13-0500
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Abstract

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete’s paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0500/-/DC1.

  • Received April 4, 2013.
  • Accepted June 10, 2013.
  • © 2013 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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October 2013, 62(10)
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Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity
Mitch T. Sitnick, Mahesh K. Basantani, Lingzhi Cai, Gabriele Schoiswohl, Cynthia F. Yazbeck, Giovanna Distefano, Vladimir Ritov, James P. DeLany, Renate Schreiber, Donna B. Stolz, Noah P. Gardner, Petra C. Kienesberger, Thomas Pulinilkunnil, Rudolf Zechner, Bret H. Goodpaster, Paul Coen, Erin E. Kershaw
Diabetes Oct 2013, 62 (10) 3350-3361; DOI: 10.2337/db13-0500

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Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity
Mitch T. Sitnick, Mahesh K. Basantani, Lingzhi Cai, Gabriele Schoiswohl, Cynthia F. Yazbeck, Giovanna Distefano, Vladimir Ritov, James P. DeLany, Renate Schreiber, Donna B. Stolz, Noah P. Gardner, Petra C. Kienesberger, Thomas Pulinilkunnil, Rudolf Zechner, Bret H. Goodpaster, Paul Coen, Erin E. Kershaw
Diabetes Oct 2013, 62 (10) 3350-3361; DOI: 10.2337/db13-0500
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