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Online Letters to the Editor

Comment on: Sitnick et al. Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity. Diabetes 2013;62:3350–3361

  1. Cedric Moro and
  2. Dominique Langin
  1. INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, and Paul Sabatier University, Toulouse, France
  1. Corresponding author: Cedric Moro, cedric.moro{at}inserm.fr.
Diabetes 2013 Dec; 62(12): e29-e29. https://doi.org/10.2337/db13-1107
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Sitnick et al. (1) provide compelling evidence that skeletal muscle–specific modulations of adipose triglyceride lipase (ATGL) expression in vivo in mice impacts intramyocellular triacylglycerol (IMTG) content with no measurable effects on other lipid species (diacylglycerols [DAG], ceramides, and long-chain acyl-coenzyme A) and insulin sensitivity. The authors speculate that the fatty acid (FA) cycle observed in cardiac muscle, with FA largely trafficking through IMTG before being consumed, may only occur in skeletal muscle during exercise. However, data from Jensen and colleagues (2) elegantly demonstrate that this cycle may be physiologically relevant in resting human skeletal muscle under normal feeding conditions. The findings in mice are also contrasting with the effect of ATGL on fat oxidation and insulin sensitivity observed in vitro in human primary myotubes (3).

The study by Sitnick et al. (1) raises a number of questions. It is first striking that long-term high-fat feeding did not raise DAG and ceramides in skeletal muscle of wild-type and skeletal muscle–specific ATGL knockout (SMAKO) mice, and that only subtle changes in skeletal muscle insulin-mediated activation of Akt were observed. As lipid-induced insulin resistance may occur without noticeable changes in canonical insulin signaling in skeletal muscle (4), future studies should specifically determine glucose uptake and insulin sensitivity in the skeletal muscle of SMAKO mice. Finally and most intriguingly, there is a remarkable discrepancy between muscle-specific (SMAKO) and whole-body genetic deletion (GAKO) of ATGL in terms of muscle insulin sensitivity (5) and glucose tolerance (6). The mechanism by which ATGL deficiency enhances whole-body glucose homeostasis despite massive IMTG accumulation remains an enigma so far. More research efforts are clearly needed to add pieces to this complex puzzle linking ATGL, IMTG, and insulin sensitivity.

ACKNOWLEDGMENTS

No potential conflicts of interest relevant to this article were reported.

  • © 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.

REFERENCES

  1. ↵
    1. Sitnick MT,
    2. Basantani MK,
    3. Cai L,
    4. et al
    . Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes 2013;62:3350–3361
  2. ↵
    1. Kanaley JA,
    2. Shadid S,
    3. Sheehan MT,
    4. Guo Z,
    5. Jensen MD
    . Relationship between plasma free fatty acid, intramyocellular triglycerides and long-chain acylcarnitines in resting humans. J Physiol 2009;587:5939–5950
    OpenUrlCrossRefPubMed
  3. ↵
    1. Badin PM,
    2. Louche K,
    3. Mairal A,
    4. et al
    . Altered skeletal muscle lipase expression and activity contribute to insulin resistance in humans. Diabetes 2011;60:1734–1742
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Høeg LD,
    2. Sjøberg KA,
    3. Jeppesen J,
    4. et al
    . Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling. Diabetes 2011;60:64–73
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Kienesberger PC,
    2. Lee D,
    3. Pulinilkunnil T,
    4. et al
    . Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J Biol Chem 2009;284:30218–30229
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Haemmerle G,
    2. Lass A,
    3. Zimmermann R,
    4. et al
    . Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006;312:734–737
    OpenUrlAbstract/FREE Full Text
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Comment on: Sitnick et al. Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity. Diabetes 2013;62:3350–3361
Cedric Moro, Dominique Langin
Diabetes Dec 2013, 62 (12) e29; DOI: 10.2337/db13-1107

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Comment on: Sitnick et al. Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity. Diabetes 2013;62:3350–3361
Cedric Moro, Dominique Langin
Diabetes Dec 2013, 62 (12) e29; DOI: 10.2337/db13-1107
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